Information

38.3D: Bone and Joint Disorders - Biology

38.3D: Bone and Joint Disorders - Biology


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

The most common bone and joint disorder are types of arthritis.

Learning Objectives

  • Describe the causes and treatments for gout, rheumatoid arthritis, and osteoarthritis

Key Points

  • Arthritis is a common disorder of synovial joints that involves inflammation of the joint; there are a few major subtypes of this disorder.
  • The most common type of arthritis is osteoarthritis, which is associated with “wear and tear” of cartilage.
  • Gout is a form of arthritis resulting from the deposit of uric acid crystals within a body joint.
  • Rheumatoid arthritis is an autoimmune disease in which the joint capsule and synovial membrane become inflamed.

Key Terms

  • synovial joints: The most common type of joint in the body, which includes a joint cavity.
  • arthritis: A joint disorder that involves inflammation in one or more joints.

Synovial joints are the most common type of joint in the body. A key structural characteristic for a synovial joint that is not seen at fibrous or cartilaginous joints is the presence of a joint cavity.

Arthritis is a common disorder of synovial joints that involves inflammation of the joint. This often results in significant joint pain, along with swelling, stiffness, and reduced joint mobility. There are more than 100 different forms of arthritis. Arthritis may arise from aging, damage to the articular cartilage, autoimmune diseases, bacterial or viral infections, or unknown (probably genetic ) causes.
Arthritis is the most common cause of disability in the USA. More than 20 million individuals with arthritis have severe limitations in function on a daily basis.

Osteoarthritis

The most common type of arthritis is osteoarthritis, which is associated with aging and “wear and tear” of the articular cartilage. Risk factors that may lead to osteoarthritis later in life include injury to a joint; jobs that involve physical labor; sports with running, twisting, or throwing actions; and being overweight.

Osteoarthritis of the Finger Joints

The formation of hard nobs at the middle finger joints (known as Bouchard’s nodes) and at the farther away finger joint (known as Heberden’s node) are a common feature of Osteoarthritis in the hands.

Osteoarthritis begins in the cartilage and eventually causes the two opposing bones to erode into each other. Osteoarthritis typically affects the weight-bearing joints, such as the back, knee and hip. There is no cure for osteoarthritis, but several treatments (surgery, lifestyle changes, medications) can help alleviate the pain.

Gout

Gout is a form of arthritis that results from the deposit of uric acid crystals within a body joint. Usually only one or a few joints are affected, such as the big toe, knee, or ankle. The attack may only last a few days, but could return to the same or another joint. Gout occurs when the body makes too much uric acid or the kidneys do not properly excrete it. A diet with excessive fructose has been implicated in raising the chances of a susceptible individual developing gout.

Rheumatoid Arthritis

Other forms of arthritis are associated with various autoimmune diseases, bacterial infections of the joint, or unknown genetic causes. Autoimmune diseases like rheumatoid arthritis produce arthritis because the immune system of the body attacks the body joints.

In rheumatoid arthritis, the joint capsule and synovial membrane become inflamed. As the disease progresses, the articular cartilage is severely damaged or destroyed, resulting in joint deformation, loss of movement, and severe disability. The most commonly involved joints are the hands, feet, and cervical spine, with corresponding joints on both sides of the body usually affected, though not always to the same extent.

Rheumatoid Arthritis: A untreated hand affected by rheumatoid arthritis.


Genetics of Bone Biology and Skeletal Disease

Genetics of Bone Biology and Skeletal Disease, Second Edition, is aimed at students of bone biology and genetics and includes general introductory chapters on bone biology and genetics. More specific disease orientated chapters comprehensively summarize the clinical, genetic, molecular, animal model, molecular pathology, diagnostic, counseling, and treatment aspects of each disorder. The book is organized into five sections that each emphasize a particular theme, general background to bone biology, general background to genetics and epigenetics, disorders of bone and joint, parathyroid and related disorders, and vitamin D and renal disorders.

The first section is specifically devoted to providing an overview of bone biology and structure, joint and cartilage biology, principles of endocrine regulation of bone, and the role of neuronal regulation and energy homeostasis. The second section reviews the principles and progress of medical genetics and epigenetics related to bone disease, including genome-wide association studies (GWAS), genomic profiling, copy number variation, prospects of gene therapy, pharmacogenomics, genetic testing and counseling, as well as the generation and utilizing of mouse models.

The third section details advances in the genetics and molecular biology of bone and joint diseases, both monogenic and polygenic, as well as skeletal dysplasias, and rarer bone disorders. The fourth section highlights the central role of the parathyroids in calcium and skeletal homeostasis by reviewing the molecular genetics of: hyperparathyroidism, hypoparathyrodism, endocrine neoplasias, and disorders of the PTH and calcium-sensing receptors. The fifth section details molecular and cellular advances across associated renal disorders such as vitamin D and rickets.

Genetics of Bone Biology and Skeletal Disease, Second Edition, is aimed at students of bone biology and genetics and includes general introductory chapters on bone biology and genetics. More specific disease orientated chapters comprehensively summarize the clinical, genetic, molecular, animal model, molecular pathology, diagnostic, counseling, and treatment aspects of each disorder. The book is organized into five sections that each emphasize a particular theme, general background to bone biology, general background to genetics and epigenetics, disorders of bone and joint, parathyroid and related disorders, and vitamin D and renal disorders.

The first section is specifically devoted to providing an overview of bone biology and structure, joint and cartilage biology, principles of endocrine regulation of bone, and the role of neuronal regulation and energy homeostasis. The second section reviews the principles and progress of medical genetics and epigenetics related to bone disease, including genome-wide association studies (GWAS), genomic profiling, copy number variation, prospects of gene therapy, pharmacogenomics, genetic testing and counseling, as well as the generation and utilizing of mouse models.

The third section details advances in the genetics and molecular biology of bone and joint diseases, both monogenic and polygenic, as well as skeletal dysplasias, and rarer bone disorders. The fourth section highlights the central role of the parathyroids in calcium and skeletal homeostasis by reviewing the molecular genetics of: hyperparathyroidism, hypoparathyrodism, endocrine neoplasias, and disorders of the PTH and calcium-sensing receptors. The fifth section details molecular and cellular advances across associated renal disorders such as vitamin D and rickets.


10 Different Types of Bone Diseases to Watch Out For

The human body contains 206 bones. Bones are living tissue, just like all the other parts of our bodies and, as such, are constantly going through a cycle of renewal. Older bone tissue is replaced with newly formed bone tissue in a process called remodeling. Much like the remodeling of a home, our skeletal structure is reinforced so that we can depend on it throughout our lives.

We commonly measure the condition of our bones by its density or “bone mass.” A bone mineral density (BMD) screening, for example, can help a physician identify the calcium content of bones – and thus how strong our bones are.

Our bone density peaks when we are young adults, typically between the ages of 25 and 30. Thereafter, as we continue to age, our bones gradually lose density. But there are ways to combat this natural loss of bone mass – such as vitamins and minerals, medications like estrogen replacement therapy, and strength-training and weight-bearing exercises.

So, what are the most common diseases or disorders that affect the bones? Here are 10 you’ll want to avoid if possible:

  1. Osteoporosis: Osteoporosis, in which low density means the bones are brittle and weak and prone to easily break, is by far the most common bone disease. It currently affects 44 million – or approximately half of all – Americans aged 50 and older. Osteoporosis strikes more women than men, and even children may be at risk of developing juvenile osteoporosis. Bone density problems may occur because the body loses too much bone tissue, makes too little of it, or some combination of both. It tends to be symptomless. That is, people with osteoporosis tend not to know they have it – until a bone fracture has them visiting a doctor who makes the diagnosis.
  2. Paget’s Disease: This is a bone disorder where the bone renewal process (remodeling) occurs too quickly, leading to bone deformities (soft, enlarged bones such as of the spine, pelvis, skull, and the long bones of the thighs and lower leg). Paget’s disease tends to occur in white adults over the age of 55 and may have a hereditary component.
  1. Bone Infection: Also called osteomyelitis, infection of bone tissue is a rare but serious condition. It can occur following a surgery, such as a hip replacement, or may spread to the bones from another part of the body. Pain, swelling, and redness are common symptoms of a bone infection, and antibiotics are a common component of treatment. In some cases, portions of the infected bone may need to be surgically removed.
  1. Osteonecrosis: Without blood, bone tissue dies, a disease called osteonecrosis. In most cases, it occurs as the result of trauma to the bone that disrupts blood flow to the bone – such as a hip fracture. Prolonged high-dose steroid use can also cause this type of bone cell death. Once the bone tissue dies, the bone weakens and collapses. Pain that gradually gets worse may indicate osteonecrosis.
  1. Bone Tumors: Bone tumors occur when the uncontrolled growth of cells occurs inside bone. These tumors can be benign or malignant, although benign (noncancerous) bone tumors that do not impinge on other bone tissue and do not spread are more common.
  1. Osteoarthritis: A chronic degenerative joint disease, osteoarthritis is the most common type of arthritis, with more than 3 million Americans diagnosed each year. Osteoarthritis occurs when the cartilage that acts as a cushion between bones breaks down and the bones rub together, causing pain, inflammation, and stiffness.
  1. Rheumatoid Arthritis: Rheumatoid arthritis is a chronic, immunodeficiency disorder in which the immune system mistakenly attacks the body’s tissues, such as the joints in the hands and feet. Unlike the wear-and-tear damage that occurs with osteoarthritis, RA affects the lining of your joints, causing a painful swelling that can eventually result in bone erosion and joint deformity.
  1. Scoliosis: This condition, in which the bones of the spine curve abnormally to the left or right, usually strikes just prior to puberty. There are approximately 3 million scoliosis diagnosis made each year in the US, although most cases are mild. In some cases, the spinal deformities get worse with time. Its cause is unknown, although a hereditary component is suspected.
  1. Low Bone Density: Also called osteopenia, it is diagnosed when a person’s bone density is lower than it should be. Low bone density can lead to osteoporosis, which causes fractures, pain, and a stooped appearance. It is important to make the changes necessary to improve bone density if you are diagnosed with osteopenia.
  2. Gout: The joints are unusually affected in people who develop gout, a common disorder in which excess uric acid crystals accumulate in the joints, causing abnormal swelling, pain, and redness. The big toe is typically noticeably swollen, but symptoms may also occur in other joints, including the ankle, foot, or knee. Gout may occur due to your diet, or if your kidneys are not properly processing uric acid.

To learn more about how we can help treat brittle bones and bone density issues to help you avoid fractures, call Total Orthopaedic Care at (954) 735-3535. To schedule an appointment, call or use our secure online appointment request form.


Role of sirtuins in bone biology: Potential implications for novel therapeutic strategies for osteoporosis

The decline in bone mass and bone strength and musculoskeletal problems associated with aging constitute a major challenge for affected individuals and the healthcare system globally. Sirtuins 1-7 (SIRT1-SIRT7) are a family of nicotinamide adenine dinucleotide-dependent deacetylases with remarkable abilities to promote longevity and counteract age-related diseases. Sirtuin knockout and transgenic models have provided novel insights into the function and signaling of these proteins in bone homeostasis. Studies have revealed that sirtuins play a critical role in normal skeletal development and homeostasis through their direct action on bone cells and that their dysregulation might contribute to different bone diseases. Preclinical studies have demonstrated that mice treated with sirtuin agonists show protection against age-related, postmenopausal, and immobilization-induced osteoporosis. These findings suggest that sirtuins could be potential targets for the modulation of the imbalance in bone remodeling and treatment of osteoporosis and other bone disorders. The aim of this review was to provide a comprehensive updated review of the current knowledge on sirtuin biology, focusing specifically on their roles in bone homeostasis and osteoporosis, and potential pharmacological interventions targeting sirtuins for the treatment of osteoporosis.

Keywords: aging bone remodeling osteoporosis sirtuins.

© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.


Citrate-Based Tannin-Bridged Bone Composites for Lumbar Fusion

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Spine Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000 P. R. China

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515 P. R. China

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 P. R. China

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Spine Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000 P. R. China

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515 P. R. China

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 P. R. China

Department of Histology and Embryology, School of Basic Medical Sciences, Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Southern Medical University, Guangzhou, 510515 P. R. China

Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, 510630 P. R. China

Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA

Abstract

Conventional bone composites consistently fail to mimic the chemical composition and integrated organic/inorganic structure of natural bone, lacking sufficient mechanics as well as inherent osteoconductivity and osteoinductivity. Through a facile surface coating process, the strong adhesive, tannic acid (TA), is adhered to the surface of the natural bone component, hydroxyapatite (HA), with and without the immobilization of in situ formed silver nanoparticles. Residual functional groups available on the immobilized TA substituents are subsequently covalently linked to the citrate-based biodegradable polymer, poly(octamethylene citrate) (POC), effectively bridging the organic and inorganic phases. Due to the synergistic effects of the tannin and citrate components, the obtained citrate-based tannin-bridged bone composites (CTBCs) exhibit vastly improved compression strengths up to 323.0 ± 21.3 MPa compared to 229.9 ± 15.6 MPa for POC-HA, and possess tunable degradation profiles, enhanced biomineralization performance, favorable biocompatibility, increased cell adhesion and proliferation, as well as considerable antimicrobial activity. In vivo study of porous CTBCs using a lumbar fusion model further confirms CTBCs' osteoconductivity and osteoinductivity, promoting bone regeneration. CTBCs possess great potential for bone regeneration applications while the immobilized TA additionally preserves surface bioconjugation sites to further tailor the bioactivity of CTBCs.

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.


RANKL in immunity

RANKL signaling is crucial for the development of various organs, including immune organs. In fact, RANKL was first reported as an activator of dendritic cells expressed by T cells [4]. The immune organs consist of immune cells and stromal cells. Studies using mice have shown that several of these cell types express RANKL or RANK, transducing signals for the development and function of the immune system as described below.

Bone marrow formation

The bone marrow is one of the primary lymphoid organs, where lymphocytes emerge and mature. Both T and B cells are born in the bone marrow and the latter cells mature in this organ. Other types of hematopoietic cells including erythrocytes reside in this space as well. Because the bone marrow space is preserved by osteoclastic bone resorption within the bone, RANKL functions as a maintainer of the bone marrow and its indwelling immune cells. In most types of osteopetrosis, the patients exhibit mild to severe hematological defects, which can lead to anemia, hemorrhage, and severe or recurrent infectious diseases [55, 56].

Thymus development

The thymus is another primary lymphoid organ where T cell progenitors undergo the positive and the negative selections for acquiring the property to distinguish non-self from self-antigens, thereby establishing self-tolerance. During negative selection, cells that strongly interact with the self-antigens expressed on major histocompatibility complex (MHC) molecules undergo apoptosis [57]. In this process, these antigens, including a portion of the tissue-specific antigens (TSAs), are expressed by medullary thymic epithelial cells (mTECs) under the control of a crucial factor, autoimmune regulator (Aire) [58, 59]. RANKL is a key cytokine for inducing Aire expression in these epithelial cells, and it is provided by lymphoid tissue inducer (LTi) cells, single positive thymocytes, Vγ5 + γδ T cells, and invariant natural killer T (iNKT) cells (Fig. 2a) [60,61,62,63]. Because thymic development is normal in mice deficient in soluble RANKL, it is suggested that membrane-bound RANKL in these cells induces mTEC development [17].

RANKL in immunity. a RANKL–RANK interaction in the development of the thymus. RANKL is produced by LTi cells, T cells, and iNKT cells and interacts with the RANK expressed on mTECs. This interaction induces the expression of Aire, resulting in the expression of TSAs on MHC molecules. The TSA–MHC complex is necessary for negative selection, the key process for establishing self-tolerance. b RANKL–RANK interaction in the lymph node development. Lymph node development begins with the interaction between LTi cells and LTo cells. LTα1β2 is expressed by LTi cells and interacts with LTβR on LTo cells, which in turn leads to the expression of RANKL on LTo cells. The expressed RANKL stimulates LTi cells to induce more LTα1β2, forming a positive feedback loop. With the stimulation of LTα1β2, some LTo cells mature into MRCs. The RANKL on LTo cells and MRCs binds to the RANK on lymphatic endothelial cells, resulting in the recruitment of macrophages. c RANKL–RANK interaction in the gastrointestinal tract. (Left) ILC3s interact with each other through RANKL and RANK. The interaction leads to the decrease of the proliferation and IL-17/IL-22 production of these cells, resulting in the suppression of excessive inflammation. (Right) RANKL–RANK interaction in M cell development. Mesenchymal cells beneath the epithelium of the gastrointestinal tract express RANKL and interact with RANK–expressing epithelial cells. These cells differentiate into morphologically and functionally unique cells called M cells. These cells enable the transfer of antigens from the lumen of gastrointestinal tract to DCs, leading to IgA production. d RANKL–RANK interaction in the skin. Keratinocytes express RANKL upon UV–irradiation. The RANKL binds to LCs in the skin. These LCs contribute to the generation of Treg cells, which decrease the skin inflammation and resolution of dermatitis in psoriasis and atopic dermatitis. e RANKL–RANK interaction in the CNS inflammation. (Left) TH17 cell cells induce the CCL20 expression of astrocytes at the blood–brain barrier via RANKL–RANK signaling. CCL20 recruits CCR6-expressing cells, including TH17 cell cells. These accumulated cells penetrate the barrier and infiltrate into the CNS to elicit inflammation. (Right) In the context of ischemic stroke, dead cells in the brain release DAMPs, which are recognized by TLRs. TLR stimulation of microglial cells leads to the production of pro-inflammatory cytokines including IL-6 and TNF-α, leading to inflammation and further cell death. RANKL–RANK signal in the microglial cells inhibits the production of these cytokines, resulting in the protection of the brain. RANKL receptor activator of NF-κB ligand, RANK receptor activator of NF-κB, LTi cell lymphoid tissue inducer cell, iNKT cell invariant natural killer T cell, mTEC medullary thymic epithelial cell, Aire autoimmune regulator, TSA tissue-specific antigen, MHC major histocompatibility complex, LTo cell lymphoid tissue organizer cell, LT lymphotoxin, LTβR lymphotoxin β receptor, MRC marginal reticular cell, ILC3 group 3 innate lymphoid cell, IL interleukin, DC dendritic cell, UV ultra violet, LC Langerhans cell, Treg cell regulatory T cell, CNS central nervous system, TH17 cell T helper 17 cell, CCL20 C-C motif chemokine ligand 20, CCR6 C-C motif chemokine receptor 6, DAMP damage-associated molecular pattern, TLR Toll-like receptor

Lymph node development

RANKL also contributes to the development and function of the secondary lymphoid organs, where immune responses take place. The LN is one such organ distributed throughout the body. LNs consist of lymphocytes and their surrounding stromal cells, establishing a complex but well-organized structure, with B and T cells localized in distinct regions [64]. LN organogenesis begins with the condensation of LTi cells, which are CD45 + CD4 + CD3 − IL-7R + RORγt + , and specific mesenchymal cells named lymphoid tissue organizer (LTo) cells. RANKL is expressed on LTi cells, LTo cells, and the descendants of the latter, marginal reticular cells (MRCs) [65, 66]. The expression of RANKL on the stromal cells in the LNs is reported to be enhanced by lymphotoxin β receptor (LTβR) signaling [67]. The RANKL signal, more likely via the membrane-bound type [17], induces the maturation of the LNs by increasing cellularity and the attraction of immune cells to the LNs [6, 65]. It was recently reported that the RANKL expressed by LTo lineage cells stimulate lymphatic endothelial cells to recruit and maintain macrophages in the LNs (Fig. 2b) [68].

Intestinal immunity

The gastrointestinal (GI) tract is the largest pathogenic bacteria entry site, with a surface area 100 times that of the body surface. In order to protect the body from these bacteria, the GI tract has developed a highly specialized defense system. Lymphocytes lacking antigen receptors, innate lymphoid cells (ILCs), are known to be abundant in the mucosal tissues and constitute a part of barrier functions by secreting cytokines [69, 70]. Group 3 ILCs, including LTi cells and ILC3s, express a transcription factor RORγt and produce high amount of cytokines IL-17 and IL-22, contributing to the homeostasis in the intestine [71, 72]. A recent study reported that ILC3s are divided into NKp46 − CCR6 − , NKp46 + CCR6 − , and NKp46 − CCR6 + cells. The expression of both RANKL and RANK showed the highest in the CCR6 + cells, which cluster within the cryptopathces [73, 74]. The proliferation and IL-17A/IL-22 expression of the CCR6 + ILC3s were suppressed by RANKL [73], indicating that these cells interact with each other in the cryptopatches to suppress excessive proliferation and inflammation (Fig. 2c).

Peyer’s patches (PPs) are lymphoid follicles beneath the intestinal epithelium. Within the epithelium covering the PPs (follicle-associated epithelium, FAE), there is a unique cell subset, M cells. Unlike their surrounding epithelial cells, M cells lack villi, but have a micro-fold structure on the apical side and a sac-like structure (the M-cell pocket) on the basal side. These cells have a high capacity for transcytosis, thus transferring the bacteria in the lumen to the DCs in the M-cell pocket. Antigen presentation to DCs via M cells results in the immune response to the transcytosed bacteria, i.e., IgA production [75]. RANKL is necessary and sufficient for M cell development, and its source during the process has been shown to be the mesenchymal cells in the lamina propria (Fig. 2c). The deficiency in soluble RANKL has not affected the development of these cells [76]. The RANKL in these mesenchymal cells also plays a role in IgA production [14].

Skin inflammation

The skin is the front line of the defense against external stimuli, and is thus equipped with a specific immune system. Langerhans cells (LCs) reside in the epidermis and are one of the key components of skin immunity [77, 78]. LCs are classified as a DC subset, with neuron-like dendrites, a high capacity for antigen presentation, and a capacity to migrate into the LNs, where LCs present antigens to T cells, thereby generating inflammatory or regulatory T (Treg) cells. RANKL has been shown to be expressed by keratinocytes upon ultra violet (UV) irradiation via the prostaglandin E receptor (EP) 4 signal [79]. The RANKL expressed by the keratinocytes interacts with RANK on LCs, resulting in the expansion of Treg cells. The increased Treg cells exert immunosuppressive effects [80], decreasing excessive inflammation in the skin (Fig. 2d). The immunosuppression induced by UV is the basis of the phototherapy used for psoriasis and atopic dermatitis, but is also can lead to carcinogenesis [81].

Inflammation in the central nervous system

The central nervous system is an immune-privileged site, which is due to the presence of the blood–brain barrier (BBB) comprised of endothelial cells, pericytes, and astrocytes. This barrier restricts the entry of cells and microorganisms [82]. A study showed that penetration of the BBB by pathogenic TH17 cells in a multiple sclerosis mouse model depended on RANKL signaling TH17 cells expressing RANKL interact with RANK-expressing astrocytes, which in turn secrete C-C motif chemokine ligand 20 (CCL20), further attracting C-C motif chemokine receptor 6 (CCR6)-expressing cells into the central nervous system (CNS) (Fig. 2e) [83].

In the brain tissue with ischemic stroke, there is an inflammation elicited by immune cells including microglial cells, macrophages, DCs, and γδ T cells [84, 85]. Reduced blood flow in the brain leads to the brain cell death, which results in the release of damage-associated molecular patterns (DAMPs) form the dead cells. These DAMPs include high mobility group box-1 (HMGB1) and peroxiredoxin (Prx), which lead to the BBB break and the stimulation of the immune cells above [86]. Clinical studies have observed that serum OPG concentration is higher in patients with ischemic stroke and is positively correlated with the severity [87]. A study showed that RANKL suppresses the production of pro-inflammatory cytokine, such as IL-6 and TNF-α, induced via Toll-like receptor 4 (TLR-4) (Fig. 2e) [84].

The course of these studies has revealed that the RANKL signal functions in various immune settings such as organogenesis, immune cell development, as well as the regulation of their function. Because RANKL serves sometimes beneficial but other times harmful, the modulation of this cytokine may be therapeutic utility in diseases affecting the immune system. Careful studies are needed to avoid the potential occurrence of side effects.


Types of Synovial Joints

Synovial joints include planar, hinge, pivot, condyloid, saddle, and ball-and-socket joints, which allow varying types of movement.

Learning Objectives

Differentiate among the six categories of joints based on shape and structure

Key Takeaways

Key Points

  • Planar joints have bones with articulating surfaces that are flat or slightly curved, allowing for limited movement pivot joints consist of the rounded end of one bone fitting into a ring formed by the other bone to allow rotational movement.
  • Hinge joints act like the hinge of a door the slightly-rounded end of one bone fits into the slightly-hollow end of the other bone one bone remains stationary.
  • Condyloid joints consist of an oval-shaped end of one bone fitting into a similarly oval-shaped hollow of another bone to allow angular movement along two axes.
  • Saddle joints include concave and convex portions that fit together and allow angular movement ball-and-socket joints include a rounded, ball-like end of one bone fitting into a cup-like socket of another bone which allows the greatest range of motion.
  • Rheumatologists diagnose and treat joint disorders, which include rheumatoid arthritis and osteoporosis.
  • Immune cells enter joints and the synovium, causing cartilage breakdown, swelling, and inflammation of the joint lining, which breaks down cartilage, resulting in bones rubbing against each other, causing pain.

Key Terms

  • condyloid joint: consists of an oval-shaped end of one bone fitting into a similarly oval-shaped hollow of another bone
  • ball-and-socket joint: consists of a rounded, ball-like end of one bone fitting into a cup-like socket of another bone, allowing the first segment to move around an indefinite number of axes which have one common center
  • rheumatoid arthritis: chronic, progressive disease in which the immune system attacks the joints characterized by pain, inflammation and swelling of the joints, stiffness, weakness, loss of mobility, and deformity

Types of Synovial Joints

Synovial joints are further classified into six different categories on the basis of the shape and structure of the joint. The shape of the joint affects the type of movement permitted by the joint. These joints can be described as planar, hinge, pivot, condyloid, saddle, or ball-and-socket joints.

Types of synovial joints: The six types of synovial joints allow the body to move in a variety of ways. (a) Pivot joints allow for rotation around an axis, such as between the first and second cervical vertebrae, which allows for side-to-side rotation of the head. (b) The hinge joint of the elbow works like a door hinge. (c) The articulation between the trapezium carpal bone and the first metacarpal bone at the base of the thumb is a saddle joint. (d) Planar (or plane) joints, such as those between the tarsal bones of the foot, allow for limited gliding movements between bones. (e) The radiocarpal joint of the wrist is a condyloid joint. (f) The hip and shoulder joints are the only ball-and-socket joints of the body.

Planar Joints

Planar joints have bones with articulating surfaces that are flat or slightly curved. These joints allow for gliding movements therefore, the joints are sometimes referred to as gliding joints. The range of motion is limited and does not involve rotation. Planar joints are found in the carpal bones in the hand and the tarsal bones of the foot, as well as between vertebrae.

Hinge Joints

In hinge joints, the slightly-rounded end of one bone fits into the slightly-hollow end of the other bone. In this way, one bone moves while the other remains stationary, similar to the hinge of a door. The elbow is an example of a hinge joint. The knee is sometimes classified as a modified hinge joint.

Pivot Joints

Pivot joints consist of the rounded end of one bone fitting into a ring formed by the other bone. This structure allows rotational movement, as the rounded bone moves around its own axis. An example of a pivot joint is the joint of the first and second vertebrae of the neck that allows the head to move back and forth. The joint of the wrist that allows the palm of the hand to be turned up and down is also a pivot joint.

Condyloid Joints

Condyloid joints consist of an oval-shaped end of one bone fitting into a similarly oval-shaped hollow of another bone. This is also sometimes called an ellipsoidal joint. This type of joint allows angular movement along two axes, as seen in the joints of the wrist and fingers, which can move both side to side and up and down.

Condyloid: The metacarpophalangeal joints in the finger are examples of condyloid joints.

Saddle Joints

Each bone in a saddle joint resembles a saddle, with concave and convex portions that fit together. Saddle joints allow angular movements similar to condyloid joints, but with a greater range of motion. An example of a saddle joint is the thumb joint, which can move back and forth and up and down it can move more freely than the wrist or fingers.

Ball-and-Socket Joints

Ball-and-socket joints possess a rounded, ball-like end of one bone fitting into a cup-like socket of another bone. This organization allows the greatest range of motion, as all movement types are possible in all directions. Examples of ball-and-socket joints are the shoulder and hip joints.

The Role of Rheumatologists

Rheumatologists are medical doctors who specialize in the diagnosis and treatment of disorders of the joints, muscles, and bones. They diagnose and treat diseases such as arthritis, musculoskeletal disorders, osteoporosis, and autoimmune diseases such as ankylosing spondylitis and rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory disorder that primarily affects the synovial joints of the hands, feet, and cervical spine. Affected joints become swollen, stiff, and painful. Although it is known that RA is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue, the cause of RA remains unknown. Immune cells from the blood enter joints and the synovium, causing cartilage breakdown, swelling, and inflammation of the joint lining. Breakdown of cartilage results in bones rubbing against each other, causing pain. RA is more common in women than men the age of onset is usually 40–50 years of age.

Ball-and-socket: The shoulder joint is an example of a ball-and-socket joint.

Rheumatologists diagnose RA on the basis of symptoms (joint inflammation and pain), X-ray and MRI imaging, and blood tests. Arthrography, a type of medical imaging of joints, uses a contrast agent, such as a dye, that is opaque to X-rays. This allows the soft tissue structures of joints, such as cartilage, tendons, and ligaments, to be visualized. An arthrogram differs from a regular X-ray by showing the surface of soft tissues lining the joint in addition to joint bones. An arthrogram allows early degenerative changes in joint cartilage to be detected before bones become affected.

There is currently no cure for RA however, rheumatologists have a number of treatment options available. Early stages can be treated by resting the affected joints, using a cane or joint splints, to minimize inflammation. When inflammation has decreased, exercise can be used to strengthen the muscles that surround the joint in order to maintain joint flexibility. If joint damage is more extensive, medications can be used to relieve pain and decrease inflammation. Anti-inflammatory drugs such as aspirin, topical pain relievers, and corticosteroid injections may be used. Surgery may be required in cases in which joint damage is severe.


Causes

The causes of skeletal dysplasias are nearly as diverse as the number of distinct disorders. Generally, however, the causes can be cataloged into three groups:

  • Genetically inherited as dominant or recessive traits or X-linked disorders
  • The result of spontaneous mutations
  • Secondary to exposure to a toxic substance or infectious agent that results in the disruption of normal skeletal development

Nearly half of the documented skeletal dysplasias are caused by a genetic mutation that makes prenatal diagnosis possible through genetic testing. For details, see common skeletal dysplasias and symptoms.


One in two Americans have a musculoskeletal condition

An estimated 126.6 million Americans (one in two adults) are affected by a musculoskeletal condition--comparable to the total percentage of Americans living with a chronic lung or heart condition--costing an estimated $213 billion in annual treatment, care and lost wages, according to a new report issued today by the United States Bone and Joint Initiative (USBJI).

Musculoskeletal disorders--conditions and injuries affecting the bones, joints and muscles--can be painful and debilitating, affecting daily quality of life, activity and productivity. "The Impact of Musculoskeletal Disorders on Americans: Opportunities for Action" outlines the prevalence and projected growth of musculoskeletal disorders in the U.S., and recommends strategies for improving patient outcomes while decreasing rising health and societal costs.

"This report provides the critical data needed to understand the magnitude of the problem, and the burden, of musculoskeletal disease in our country," said David Pisetsky, MD, USBJI president, and professor of medicine and immunology at Duke University Medical School. "The number of visits to physicians for these disorders, the cost of treating them, and the indirect costs associated with pain and loss of mobility, are proportionately much higher than the resources currently being allocated to combat these conditions and injuries."

"As a nation, we need to establish greater funding for musculoskeletal research, improve our understanding and strategies for prevention and treatment of these injuries and conditions, and ensure that more adults and children receive appropriate treatment sooner, and on an ongoing basis, to ensure quality of life and productivity," said Stuart L. Weinstein, MD, co-chair of the report's Steering Committee and a professor of orthopaedics and rehabilitation at the University of Iowa Hospitals and Clinics.

Prevalence and predictions

According to the report, the most prevalent musculoskeletal disorders are arthritis and related conditions back and neck pain injuries from falls, work, military service and sports and osteoporosis, a loss of bone density increasing fracture risk, primarily in older women. An estimated 126.6 million Americans were living with a musculoskeletal disorder in 2012. More specifically:

  • Arthritis is the most common cause of disability, with 51.8 million--half of U.S. adults age 65 and older--suffering from the disease.
  • With the aging of the American population, the report projects arthritis prevalence to increase to 67 million people, or 25 percent of the adult population, by 2030.
  • Arthritis is not just a disease for older Americans, with two-thirds of arthritis sufferers under age 65.
  • Back and neck pain affects nearly one in three, or 75.7 million adults.
  • Osteoporosis affects 10 million Americans, with 19 million more (mostly women) at risk for the disease.
  • One in two women and one in four men over the age of 50 will have an osteoporosis-related fracture, and 20 percent of hip fracture patients over age 50 will die within one year of their injury.

Cost and health care impact

The burden of musculoskeletal conditions is significant in terms of treatment and care, as well as the impact upon of quality of life, mobility, and productivity, and resulting in fewer days at work and in school. In 2011, the annual U.S. cost for treatment and lost wages related to musculoskeletal disorders was $213 billion, or 1.4 percent of the country's gross domestic product (GDP). When adding the burden of other conditions affecting persons with musculoskeletal conditions such as diabetes, heart disease and obesity, the total indirect and direct costs rose to $874 billion, or 5.7 percent of the GDP in 2015.

Other data on the costs of musculoskeletal diseases and injuries include:

  • Eighteen percent of all health care visits in 2010 were related to musculoskeletal conditions, including 52 million visits for low back pain, and 66 million for bone and joint injuries, including 14 million visits for childhood injuries.
  • Arthritis and rheumatoid conditions resulted in an estimated 6.7 million annual hospitalizations.
  • The average annual cost per person for treatment of a musculoskeletal condition is $7,800.
  • The estimated annual cost for medical care to treat all forms of arthritis and joint pain was $580.9 billion, which represented a 131 percent increase (in 2011 dollars) over 2000.
  • In 2012, 25.5 million people lost an average of 11.4 days of work due to back or neck pain, for a total of 290.8 million lost workdays in 2012 alone.
  • Among children and adolescents, musculoskeletal conditions are surpassed only by respiratory infections as a cause of missed school days.

Opportunities for action

The report provides recommendations to curb the tremendous economic and societal costs of musculoskeletal disorders, including:

  • Accelerating research that compares treatment alternatives, develops new treatments and evaluates possible preventative approaches.
  • Improving understanding of the role of behavior change in prevention and treatment, including weight loss and self-management of conditions once they arise.
  • Ensuring that a higher percentage of the affected population receives access to evidence-based treatments.
  • Implementing proven prevention strategies for sports injuries, workplace injuries, and injuries in the military.
  • Ensuring that all children with chronic medical and musculoskeletal problems have access to care.
  • Promoting better coordination between physicians and other health care providers treating musculoskeletal disorders: primary care physicians, specialists, physical therapists, chiropractors, etc.
  • Ensuring that health care providers, especially primary care physicians, have the appropriate training to diagnose, and if necessary, refer patients for appropriate treatment.
  • Addressing data limitations, and improve systems, to improve our understanding of these conditions and how best to screen, diagnose and treat them. This includes the impact of sex and gender on musculoskeletal disorders and responses to treatment, and tracking pediatric patients through adulthood to determine the lifelong burden of musculoskeletal disease.

"If we continue on our current trajectory, we are choosing to accept more prevalence and incidence of these disorders, spiraling costs, restricted access to needed services, and less success in alleviating pain and suffering -- a high cost," said Edward H. Yelin, PhD, co-chair of the report's steering committee, and professor of medicine and health policy at the University of California, San Francisco. "The time to act to change this scenario to one with more evidence-based interventions and effective treatments, while simultaneously focusing on prevention, doing better by our society and economy, is now."