Review

Authors: J L Whittaker, J Runhaar, S Bierma-Zeinstra...

Prevention is an attractive solution for the staggering and increasingly unmanageable burden of osteoarthritis. Despite this, the field of osteoarthritis prevention is relatively immature. To date, most of what is known about preventing osteoarthritis and risk factors for osteoarthritis is relative to the disease (underlying biology and pathophysiology) of osteoarthritis, with few studies considering risk factors for osteoarthritis illness, the force driving the personal, financial and societal burden. In this narrative review we will discuss what is known about osteoarthritis prevention, propose actionable prevention strategies related to obesity and joint injury which have emerged as important modifiable risk factors, identify where evidence is lacking, and give insight into what might be possible in terms of prevention by focussing on a lifespan approach to the illness of osteoarthritis, as opposed to a structural disease of the elderly. By targeting a non-specialist audience including scientists, clinicians, students, industry employees and others that are interested in osteoarthritis but who do not necessarily focus on osteoarthritis, the goal is to generate discourse and motivate inquiry which propel the field of osteoarthritis prevention into the mainstream.

Topics: Bone Malalignment; Exercise; Genetic Predisposition to Disease; Health Behavior; Health Promotion; Humans; Joints; Muscle Weakness; Osteoarthritis; Overweight; Patient Education as Topic; Risk Factors; Sex Factors

PubMed: 34560260
DOI: 10.1016/j.joca.2021.06.015

Review

Authors: Nicolas V Jaumard, William C Welch, Beth A Winkelstein...

The facet joint is a crucial anatomic region of the spine owing to its biomechanical role in facilitating articulation of the vertebrae of the spinal column. It is a diarthrodial joint with opposing articular cartilage surfaces that provide a low friction environment and a ligamentous capsule that encloses the joint space. Together with the disc, the bilateral facet joints transfer loads and guide and constrain motions in the spine due to their geometry and mechanical function. Although a great deal of research has focused on defining the biomechanics of the spine and the form and function of the disc, the facet joint has only recently become the focus of experimental, computational and clinical studies. This mechanical behavior ensures the normal health and function of the spine during physiologic loading but can also lead to its dysfunction when the tissues of the facet joint are altered either by injury, degeneration or as a result of surgical modification of the spine. The anatomical, biomechanical and physiological characteristics of the facet joints in the cervical and lumbar spines have become the focus of increased attention recently with the advent of surgical procedures of the spine, such as disc repair and replacement, which may impact facet responses. Accordingly, this review summarizes the relevant anatomy and biomechanics of the facet joint and the individual tissues that comprise it. In order to better understand the physiological implications of tissue loading in all conditions, a review of mechanotransduction pathways in the cartilage, ligament and bone is also presented ranging from the tissue-level scale to cellular modifications. With this context, experimental studies are summarized as they relate to the most common modifications that alter the biomechanics and health of the spine-injury and degeneration. In addition, many computational and finite element models have been developed that enable more-detailed and specific investigations of the facet joint and its tissues than are provided by experimental approaches and also that expand their utility for the field of biomechanics. These are also reviewed to provide a more complete summary of the current knowledge of facet joint mechanics. Overall, the goal of this review is to present a comprehensive review of the breadth and depth of knowledge regarding the mechanical and adaptive responses of the facet joint and its tissues across a variety of relevant size scales.

Topics: Biomechanical Phenomena; Cartilage, Articular; Cervical Vertebrae; Computer Simulation; Finite Element Analysis; Humans; Intervertebral Disc Displacement; Joint Capsule; Ligaments, Articular; Lumbar Vertebrae; Mechanotransduction, Cellular; Range of Motion, Articular; Spine; Stress, Mechanical; Total Disc Replacement; Zygapophyseal Joint

PubMed: 21823749
DOI: 10.1115/1.4004493

Review

Authors: Mohammad Yunus Ansari, Nashrah Ahmad, Tariq M Haqqi...

Osteoarthritis (OA) is the most prevalent joint degenerative disease leading to irreversible structural and functional changes in the joint and is a major cause of disability and reduced life expectancy in ageing population. Despite the high prevalence of OA, there is no disease modifying drug available for the management of OA. Oxidative stress, a result of an imbalance between the production of reactive oxygen species (ROS) and their clearance by antioxidant defense system, is high in OA cartilage and is a major cause of chronic inflammation. Inflammatory mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are highly upregulated in OA joints and induce ROS production and expression of matrix degrading proteases leading to cartilage extracellular matrix degradation and joint dysfunction. ROS and inflammation are interdependent, each being the target of other and represent ideal target/s for the treatment of OA. Plant polyphenols possess potent antioxidant and anti-inflammatory properties and can inhibit ROS production and inflammation in chondrocytes, cartilage explants and in animal models of OA. The aim of this review is to discuss the chondroprotective effects of polyphenols and modulation of different molecular pathways associated with OA pathogenesis and limitations and future prospects of polyphenols in OA treatment.

Topics: Animals; Anti-Infective Agents; Antioxidants; Antirheumatic Agents; Humans; Inflammation Mediators; Joints; Osteoarthritis; Oxidative Stress; Polyphenols; Reactive Oxygen Species; Signal Transduction

PubMed: 32768946
DOI: 10.1016/j.biopha.2020.110452

Review

Authors: Margaret H Chang, Robert C Fuhlbrigge, Peter A Nigrovic...

In rheumatoid arthritis, juvenile idiopathic arthritis and other forms of inflammatory arthritis, the immune system targets certain joints but not others. The pattern of joints affected varies by disease and by individual, with flares most commonly involving joints that were previously inflamed. This phenomenon, termed joint-specific memory, is difficult to explain by systemic immunity alone. Mechanisms of joint-specific memory include the involvement of synovial resident memory T cells that remain in the joint during remission and initiate localized disease recurrence. In addition, arthritis-induced durable changes in synovial fibroblasts and macrophages can amplify inflammation in a site-specific manner. Together with ongoing systemic processes that promote extension of arthritis to new joints, these local factors set the stage for a stepwise progression in disease severity, a paradigm for arthritis chronicity that we term the joint accumulation model. Although durable drug-free remission through early treatment remains elusive for most forms of arthritis, the joint accumulation paradigm defines new therapeutic targets, emphasizes the importance of sustained treatment to prevent disease extension to new joints, and identifies a rolling window of opportunity for altering the natural history of arthritis that extends well beyond the initiation phase of disease.

Topics: Humans; Memory T Cells; Arthritis, Rheumatoid; Joints; Immunologic Memory; Disease Progression; Animals; Synovial Membrane; Arthritis

PubMed: 38600215
DOI: 10.1038/s41584-024-01107-7

Review

Authors: Joanna E Salva, Amy E Merrill

Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the fluid-filled synovial space between the bones, are found in high-mobility regions and are the most common type of joint. Cartilaginous joints such as the intervertebral disc unite adjacent bones through either a hyaline cartilage or a fibrocartilage intermediate. Fibrous joints, which include the cranial sutures, form a direct union between bones through fibrous connective tissue. We describe how the distinct morphologic and histogenic characteristics of these joint classes are established during embryonic development. Collectively, these studies reveal that despite the heterogeneity of joint strength and mobility, joint development throughout the skeleton utilizes common signaling networks via long-range morphogen gradients and direct cell-cell contact. This suggests that different joint types represent specialized variants of homologous developmental modules. Identifying the unifying aspects of the signaling networks between joint classes allows a more complete understanding of the signaling code for joint formation, which is critical to improving strategies for joint regeneration and repair. Developmental Dynamics 246:262-274, 2017. © 2016 Wiley Periodicals, Inc.

Topics: Animals; Cartilage, Articular; Gene Regulatory Networks; Humans; Joint Capsule; Joints; Morphogenesis; Regeneration; Signal Transduction

PubMed: 27859991
DOI: 10.1002/dvdy.24472

Review

Authors: Jingxiong Huang, Chengcheng Liao, Jian Yang...

The vascular and lymphatic systems are integral to maintaining skeletal homeostasis and responding to pathological conditions in bone and joint tissues. This review explores the interplay between blood vessels and lymphatic vessels in bones and joints, focusing on their roles in homeostasis, regeneration, and disease progression. Type H blood vessels, characterized by high expression of CD31 and endomucin, are crucial for coupling angiogenesis with osteogenesis, thus supporting bone homeostasis and repair. These vessels facilitate nutrient delivery and waste removal, and their dysfunction can lead to conditions such as ischemia and arthritis. Recent discoveries have highlighted the presence and significance of lymphatic vessels within bone tissue, challenging the traditional view that bones are devoid of lymphatics. Lymphatic vessels contribute to interstitial fluid regulation, immune cell trafficking, and tissue repair through lymphangiocrine signaling. The pathological alterations in these networks are closely linked to inflammatory joint diseases, emphasizing the need for further research into their co-regulatory mechanisms. This comprehensive review summarizes the current understanding of the structural and functional aspects of vascular and lymphatic networks in bone and joint tissues, their roles in homeostasis, and the implications of their dysfunction in disease. By elucidating the dynamic interactions between these systems, we aim to enhance the understanding of their contributions to skeletal health and disease, potentially informing the development of targeted therapeutic strategies.

Topics: Humans; Homeostasis; Bone and Bones; Lymphatic Vessels; Animals; Joints; Blood Vessels; Joint Diseases

PubMed: 39324127
DOI: 10.3389/fendo.2024.1465816

Review

Authors: Rebekah S Decker

Within each synovial joint, the articular cartilage is uniquely adapted to bear dynamic compressive loads and shear forces throughout the joint's range of motion. Injury and age-related degeneration of the articular cartilage often lead to significant pain and disability, as the intrinsic repair capability of the tissue is extremely limited. Current surgical and biological treatment options have been unable to restore cartilage de novo. Before successful clinical cartilage restoration strategies can be developed, a better understanding of how the cartilage forms during normal development is essential. This review focuses on recent progress made towards addressing key questions about articular cartilage morphogenesis, including the origin of synovial joint progenitor cells, postnatal development and growth of the tissue. These advances have provided novel insight into fundamental questions about the developmental biology of articular cartilage, as well as potential cell sources that may participate in joint response to injury.

Topics: Aging; Animals; Cartilage, Articular; Embryonic Development; Humans; Joints; Morphogenesis; Stem Cells

PubMed: 27771363
DOI: 10.1016/j.semcdb.2016.10.005

Authors: Miki Maemura, Masanobu Morita, Seiryo Ogata...

The physiological functions of supersulfides, inorganic and organic sulfides with sulfur catenation, have been extensively studied. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulfide synthase. This study aimed to investigate the role of supersulfides in joint homeostasis and bone regeneration. Using Cars2 mutant mice, in which the KIIK motif of CARS2 essential for supersulfide production was replaced with AINK, we evaluated the role of supersulfides in fracture healing and cartilage homeostasis during osteoarthritis (OA). Tibial fracture surgery was performed on the wild-type (Cars2) and Cars2 mice littermates. Bulk RNA-seq analysis for the osteochondral regeneration in the fracture model showed increased inflammatory markers and reduced osteogenic factors, indicative of impaired bone regeneration, in Cars2 mice. Destabilization of the medial meniscus (DMM) surgery was performed to produce the mouse OA model. Histological analyses with Osteoarthritis Research Society International and synovitis scores revealed accelerated OA progression in Cars2 mice compared with that in Cars2 mice. To assess the effects of supersulfides on OA progression, glutathione trisulfide (GSSSG) or saline was periodically injected into the mouse knee joints after the DMM surgery. Thus, supersulfides derived from CARS2 and GSSSG exogenously administered significantly inhibited inflammation and lipid peroxidation of the joint cartilage, possibly through suppression of ferroptosis, during OA development. This study represents a significant advancement in understanding anti-inflammatory and anti-oxidant functions of supersulfides in skeletal tissues and may have a clinical relevance for the bone healing and OA therapeutics.

Topics: Sulfides; Homeostasis; Joints; Bone Regeneration; Amino Acyl-tRNA Synthetases; Animals; Mice; Mice, Mutant Strains; Osteoarthritis; Glutathione; Knee Joint; Fractures, Bone; Cartilage; Male

PubMed: 39983344
DOI: 10.1016/j.redox.2025.103545

Authors: Lei Li, Jingcheng Chen, Shaoming Sun...

PURPOSE

This study introduces a transferable alignment-free adaptive joint torque measurement (AFAJTM) system designed to resolve inconsistencies in torque measurements caused by misalignment between dynamometer and joint rotational axes, improving accuracy and reliability in joint torque assessment.

METHOD

This study presents the design and control methodology of an alignment free adaptive joint torque measurement system. An elbow joint torque measurement device (EJTMD) was developed, and its torque consistency and repeatability were evaluated at various misalignment positions using a joint simulation model. Clinical experiments compared torque measurements between the EJTMD and a traditional standard dynamometer during maximum voluntary contraction (MVC) tests at different misalignment positions.

RESULT

The simulation test results demonstrate that the AFAJTM system can achieve high-precision torque measurements, with measurement errors controlled within ± 0.5 Nm at various misalignment positions. Clinical experiment data show that the EJTMD exhibits high consistency in torque measurements compared to the traditional standard dynamometer across five different misalignment positions, with strong repeatability and reliability.

CONCLUSION

The AFAJTM system provides a novel solution for joint torque measurement under human-machine axis misalignment conditions, a solution that eliminates the need for axis alignment, effectively overcoming the limitations of traditional measurement devices. This system can be widely applied in various devices that require joint torque measurement, demonstrating excellent adaptability and high-precision measurement capabilities.

Topics: Torque; Humans; Equipment Design; Elbow Joint; Reproducibility of Results; Male; Joints; Adult

PubMed: 39994741
DOI: 10.1186/s12938-025-01356-x

Review

Authors: Sofija Semenistaja, Sandra Skuja, Anda Kadisa...

Osteoarthritis (OA) is a chronic, progressive, severely debilitating, and multifactorial joint disease that is recognized as the most common type of arthritis. During the last decade, it shows an incremental global rise in prevalence and incidence. The interaction between etiologic factors that mediate joint degradation has been explored in numerous studies. However, the underlying processes that induce OA remain obscure, largely due to the variety and complexity of these mechanisms. During synovial joint dysfunction, the osteochondral unit undergoes cellular phenotypic and functional alterations. At the cellular level, the synovial membrane is influenced by cartilage and subchondral bone cleavage fragments and extracellular matrix (ECM) degradation products from apoptotic and necrotic cells. These "foreign bodies" serve as danger-associated molecular patterns (DAMPs) that trigger innate immunity, eliciting and sustaining low-grade inflammation in the synovium. In this review, we explore the cellular and molecular communication networks established between the major joint compartments-the synovial membrane, cartilage, and subchondral bone of normal and OA-affected joints.

Topics: Humans; Cartilage, Articular; Osteoarthritis; Joints; Synovial Membrane; Bone and Bones; Inflammation

PubMed: 36835530
DOI: 10.3390/ijms24044120