Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage–bone crosstalk

In diarthrodial joints, the articular cartilage, calcified cartilage, and subchondral cortical and trabecular bone form a biocomposite — referred to as the osteochondral unit — that is uniquely adapted to the transfer of load. During the evolution of the osteoarthritic process the compositions, functional properties, and structures of these tissues undergo marked alterations. Although pathological processes might selectively target a single joint tissue, ultimately all of the components of the osteochondral unit will be affected because of their intimate association, and thus the biological and physical crosstalk among them is of great importance. The development of targeted therapies against the osteoarthritic processes in cartilage or bone will, therefore, require an understanding of the state of these joint tissues at the time of the intervention. Importantly, these interventions will not be successful unless they are applied at the early stages of disease before considerable structural and functional alterations occur in the osteochondral unit. This Review describes the changes that occur in bone and cartilage during the osteoarthritic process, and highlights strategies for how this knowledge could be applied to develop new therapeutic interventions for osteoarthritis.

[1]  J. Landells The bone cysts of osteoarthritis. , 1953, The Journal of bone and joint surgery. British volume.

[2]  D. Lamb,et al.  The cysts of osteoarthritis of the hip; a radiological and pathological study. , 1955, The Journal of bone and joint surgery. British volume.

[3]  T. Brower,et al.  The Diffusion of Dyes Through Articular Cartilage in Vivo , 1962 .

[4]  P. Bullough,et al.  Permeability of articular cartilage. , 1968, Nature.

[5]  P. Bullough,et al.  The vascularity and remodelling of subchondrial bone and calcified cartilage in adult human femoral and humeral heads. An age- and stress-related phenomenon. , 1977, Journal of Bone and Joint Surgery-british Volume.

[6]  T D Brown,et al.  Finite element studies of some juxtarticular stress changes due to localized subchondral stiffening. , 1984, Journal of biomechanics.

[7]  E. Radin,et al.  Effects of mechanical loading on the tissues of the rabbit knee , 1984, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[8]  R. Rose,et al.  Role of Subchondral Bone in the Initiation and Progression of Cartilage Damage , 1986, Clinical orthopaedics and related research.

[9]  B. Weightman,et al.  Mechanical and biochemical properties of human articular cartilage in osteoarthritic femoral heads and in autopsy specimens. , 1986, The Journal of bone and joint surgery. British volume.

[10]  P. C. Jackson,et al.  99mTc HMDP bone scanning in generalised nodal osteoarthritis. II. The four hour bone scan image predicts radiographic change. , 1986, Annals of the rheumatic diseases.

[11]  V. Mow,et al.  Tensile properties of human knee joint cartilage. II. Correlations between weight bearing and tissue pathology and the kinetics of swelling , 1987, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[12]  A. Wilson,et al.  Transient osteoporosis: transient bone marrow edema? , 1988, Radiology.

[13]  L. Draganich,et al.  The effect of marginal osteophytes on reduction of varus-valgus instability in osteoarthritic knees. , 1990, Arthritis and rheumatism.

[14]  P Young,et al.  Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy. , 1993, Annals of the rheumatic diseases.

[15]  D. Burr,et al.  Microcracks in articular calcified cartilage of human femoral heads. , 1992, Archives of pathology & laboratory medicine.

[16]  D B Burr,et al.  Increased intracortical remodeling following fatigue damage. , 1993, Bone.

[17]  L. Sokoloff Microcracks in the calcified layer of articular cartilage. , 1993, Archives of pathology & laboratory medicine.

[18]  D. Burr,et al.  The involvement of subchondral mineralized tissues in osteoarthrosis: Quantitative microscopic evidence , 1997, Microscopy research and technique.

[19]  A. Gatherer,et al.  Sarcoma of the Larynx , 1958, The Journal of Laryngology & Otology.

[20]  G Boivin,et al.  Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. , 1997, Bone.

[21]  W. B. van den Berg,et al.  Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation. , 1998, Osteoarthritis and cartilage.

[22]  D. Nelson,et al.  Periarticular osteoporosis in osteoarthritis of the knee. , 1998, The Journal of rheumatology.

[23]  J. Pelletier,et al.  Osteoblast-like cells from human subchondral osteoarthritic bone demonstrate an altered phenotype in vitro: possible role in subchondral bone sclerosis. , 1998, Arthritis and rheumatism.

[24]  W. B. van den Berg,et al.  Osteoarthritis-like changes in the murine knee joint resulting from intra-articular transforming growth factor-beta injections. , 2000, Osteoarthritis and cartilage.

[25]  H. Imhof,et al.  Subchondral Bone and Cartilage Disease: A Rediscovered Functional Unit , 2000, Investigative radiology.

[26]  M. Zanetti,et al.  Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. , 2000, Radiology.

[27]  H. Frost From Wolff's law to the Utah paradigm: Insights about bone physiology and its clinical applications , 2001, The Anatomical record.

[28]  D. R. Sumner,et al.  A decreased subchondral trabecular bone tissue elastic modulus is associated with pre‐arthritic cartilage damage , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[29]  D. Zukor,et al.  Sites of collagenase cleavage and denaturation of type II collagen in aging and osteoarthritic articular cartilage and their relationship to the distribution of matrix metalloproteinase 1 and matrix metalloproteinase 13. , 2002, Arthritis and rheumatism.

[30]  W. B. van den Berg,et al.  Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair , 2002, The Journal of Immunology.

[31]  M. Hanes,et al.  A comparative analysis of bone and cartilage metabolism in two strains of guinea-pig with varying degrees of naturally occurring osteoarthritis. , 2002, Osteoarthritis and cartilage.

[32]  R. Brand,et al.  Apparent Spontaneous Joint Restoration in Hip Osteoarthritis , 2002, Clinical orthopaedics and related research.

[33]  W. B. van den Berg,et al.  Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. , 2003, Arthritis and rheumatism.

[34]  Wei Li,et al.  Bone Marrow Edema and Its Relation to Progression of Knee Osteoarthritis , 2003, Annals of Internal Medicine.

[35]  K. Messner,et al.  Meniscectomy leads to an early increase in subchondral bone plate thickness in the rabbit knee , 2003, Acta orthopaedica Scandinavica.

[36]  P. Bullough The role of joint architecture in the etiology of arthritis. , 2004, Osteoarthritis and cartilage.

[37]  D. Walsh Angiogenesis in osteoarthritis and spondylosis: successful repair with undesirable outcomes , 2004, Current opinion in rheumatology.

[38]  D. Heinegård,et al.  Altered patterns and synthesis of extracellular matrix macromolecules in early osteoarthritis. , 2004, Matrix biology : journal of the International Society for Matrix Biology.

[39]  S Gary Firestein,et al.  Kelley's Textbook of Rheumatology , 2004 .

[40]  D. Eyre,et al.  Collagens and cartilage matrix homeostasis. , 2004, Clinical orthopaedics and related research.

[41]  H. Weinans,et al.  Adaptation of subchondral bone in osteoarthritis. , 2004, Biorheology.

[42]  D. Burr,et al.  Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis. , 2004, Osteoarthritis and cartilage.

[43]  C. Buckland-Wright Subchondral bone changes in hand and knee osteoarthritis detected by radiography. , 2004, Osteoarthritis and cartilage.

[44]  Laura W. Bancroft,et al.  Cysts, geodes, and erosions. , 2004, Radiologic clinics of North America.

[45]  I. Palacios,et al.  Histopathological correlation of cartilage swelling detected by magnetic resonance imaging in early experimental osteoarthritis. , 2004, Osteoarthritis and cartilage.

[46]  Y. Henrotin,et al.  Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes. , 2005, Osteoarthritis and cartilage.

[47]  D. Felson,et al.  Osteophytes and progression of knee osteoarthritis. , 2005, Rheumatology.

[48]  T. Spector,et al.  Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173] , 2005, Arthritis Research & Therapy.

[49]  J. Parellada,et al.  MRI of bone marrow edema-like signal in the pathogenesis of subchondral cysts. , 2006, Osteoarthritis and cartilage.

[50]  Ali Guermazi,et al.  Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis. , 2006, Arthritis and rheumatism.

[51]  S. Ott,et al.  Mineral Changes in Osteoporosis: A Review , 2006, Clinical orthopaedics and related research.

[52]  J. Mcclure,et al.  The normal human chondro-osseous junctional region: evidence for contact of uncalcified cartilage with subchondral bone and marrow spaces , 2006, BMC musculoskeletal disorders.

[53]  S. Jimenez,et al.  Osteoarthritis cartilage histopathology: grading and staging. , 2006, Osteoarthritis and cartilage.

[54]  T. Spector,et al.  Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. , 2006, Arthritis and rheumatism.

[55]  S. Stover,et al.  Subchondral bone failure in overload arthrosis: a scanning electron microscopic study in horses. , 2006, Journal of musculoskeletal & neuronal interactions.

[56]  D. Walsh,et al.  Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis. , 2007, Osteoarthritis and cartilage.

[57]  E. Hunziker,et al.  The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development. , 2007, Osteoarthritis and cartilage.

[58]  C. Bingham,et al.  A 2 yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients. , 2006, Rheumatology.

[59]  P. M. van der Kraan,et al.  Osteophytes: relevance and biology. , 2007, Osteoarthritis and cartilage.

[60]  C Buckland-Wright,et al.  Osteophytes, juxta-articular radiolucencies and cancellous bone changes in the proximal tibia of patients with knee osteoarthritis. , 2007, Osteoarthritis and cartilage.

[61]  D. Walsh,et al.  Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis , 2007, Annals of the rheumatic diseases.

[62]  K. Gelse,et al.  Hypoxia and osteoarthritis: how chondrocytes survive hypoxic environments , 2007, Current opinion in rheumatology.

[63]  J F Beary,et al.  Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period , 2007, Annals of the rheumatic diseases.

[64]  D. Felson,et al.  The association of bone attrition with knee pain and other MRI features of osteoarthritis , 2007, Annals of the rheumatic diseases.

[65]  A. F. Mendes,et al.  Facilitative Glucose Transporters in Articular Chondrocytes , 2008 .

[66]  Su-Jeong Lee,et al.  Clinical value of 99mTc-methylene diphosphonate (MDP) bone single photon emission computed tomography (SPECT) in patients with knee osteoarthritis , 2008 .

[67]  H Weinans,et al.  Cartilage damage pattern in relation to subchondral plate thickness in a collagenase-induced model of osteoarthritis. , 2008, Osteoarthritis and cartilage.

[68]  C. Christiansen,et al.  Relationships between biochemical markers of bone and cartilage degradation with radiological progression in patients with knee osteoarthritis receiving risedronate: the Knee Osteoarthritis Structural Arthritis randomized clinical trial. , 2008, Osteoarthritis and cartilage.

[69]  A. Boyde,et al.  High resolution microscopic survey of third metacarpal articular calcified cartilage and subchondral bone in the juvenile horse: Possible implications in chondro‐osseous disease , 2008, Microscopy research and technique.

[70]  D. Walsh,et al.  Angiogenesis in osteoarthritis , 2008, Current opinion in rheumatology.

[71]  V. Castronovo,et al.  Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritic subchondral bone. , 2008, Arthritis and rheumatism.

[72]  Ali Guermazi,et al.  Prevalence of bone attrition on knee radiographs and MRI in a community-based cohort. , 2008, Osteoarthritis and cartilage.

[73]  C. Poole,et al.  Primary cilia in osteoarthritic chondrocytes: From chondrons to clusters , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[74]  D J Hunter,et al.  Strong association of MRI meniscal derangement and bone marrow lesions in knee osteoarthritis: data from the osteoarthritis initiative. , 2009, Osteoarthritis and cartilage.

[75]  A. Guermazi,et al.  MRI-based semiquantitative assessment of subchondral bone marrow lesions in osteoarthritis research. , 2009, Osteoarthritis and cartilage.

[76]  A. Simpson,et al.  Chondrocyte survival in articular cartilage: the influence of subchondral bone in a bovine model. , 2009, The Journal of bone and joint surgery. British volume.

[77]  S. Goldring Role of bone in osteoarthritis pathogenesis. , 2009, The Medical clinics of North America.

[78]  S. Goldring Needs and opportunities in the assessment and treatment of osteoarthritis of the knee and hip: the view of the rheumatologist. , 2009, The Journal of bone and joint surgery. American volume.

[79]  S. Doty,et al.  In situ measurement of transport between subchondral bone and articular cartilage , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[80]  R. Coleman,et al.  Whole-body bone scintigraphy provides a measure of the total-body burden of osteoarthritis for the purpose of systemic biomarker validation. , 2009, Arthritis and rheumatism.

[81]  M. Benjamin,et al.  The enthesis organ concept and its relevance to the spondyloarthropathies. , 2009, Advances in experimental medicine and biology.

[82]  B. Manaster Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology , 2009 .

[83]  J. Argenson,et al.  Advanced hip osteoarthritis: magnetic resonance imaging aspects and histopathology correlations. , 2010, Osteoarthritis and cartilage.

[84]  S. Goldring,et al.  Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis , 2010, Annals of the New York Academy of Sciences.

[85]  Matthias Aurich,et al.  Proliferative Remodeling of the Spatial Organization of Human Superficial Chondrocytes Distant from Focal Early Osteoarthritis Accessed Terms of Use Detailed Terms Proliferative Re-modeling of the Spatial Organization of Human Superficial Chondrocytes Distant to Focal Early Osteoarthritis (oa) Nih P , 2022 .

[86]  D. Felson,et al.  Contrast-enhanced MRI of subchondral cysts in patients with or at risk for knee osteoarthritis: the MOST study. , 2010, European journal of radiology.

[87]  E. Eriksen,et al.  Cellular mechanisms of bone remodeling , 2010, Reviews in Endocrine and Metabolic Disorders.

[88]  M. Lotz,et al.  Correction: Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment , 2010 .

[89]  F. Cicuttini,et al.  The association between subchondral bone cysts and tibial cartilage volume and risk of joint replacement in people with knee osteoarthritis: a longitudinal study , 2010, Arthritis research & therapy.

[90]  L. Sharma,et al.  Within‐subregion relationship between bone marrow lesions and subsequent cartilage loss in knee osteoarthritis , 2010, Arthritis care & research.

[91]  Ali Guermazi,et al.  Subchondral bone attrition may be a reflection of compartment-specific mechanical load: the MOST Study , 2009, Annals of the rheumatic diseases.

[92]  Carol Muehleman,et al.  Vulnerability of the superficial zone of immature articular cartilage to compressive injury. , 2010, Arthritis and rheumatism.

[93]  D. Felson,et al.  Subchondral cystlike lesions develop longitudinally in areas of bone marrow edema-like lesions in patients with or at risk for knee osteoarthritis: detection with MR imaging--the MOST study. , 2010, Radiology.

[94]  Jonghwan Kim,et al.  Hypoxia-inducible factor-2α is a catabolic regulator of osteoarthritic cartilage destruction , 2010, Nature Medicine.

[95]  Kozo Nakamura,et al.  Transcriptional regulation of endochondral ossification by HIF-2α during skeletal growth and osteoarthritis development , 2010, Nature Medicine.

[96]  D. Walsh,et al.  Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis , 2010, Rheumatology.

[97]  Jacob N. Israelachvili,et al.  Adaptive mechanically controlled lubrication mechanism found in articular joints , 2011, Proceedings of the National Academy of Sciences.

[98]  Ali Guermazi,et al.  Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study , 2011, Annals of the rheumatic diseases.

[99]  D. Hunter,et al.  Emerging drugs for osteoarthritis , 2011, Expert opinion on emerging drugs.

[100]  Jinhu Xiong,et al.  Matrix-embedded cells control osteoclast formation , 2011, Nature Medicine.

[101]  D. Walsh,et al.  Increased vascular penetration and nerve growth in the meniscus: a potential source of pain in osteoarthritis , 2010, Annals of the rheumatic diseases.

[102]  Frank Beier,et al.  Emerging Frontiers in cartilage and chondrocyte biology. , 2011, Best practice & research. Clinical rheumatology.

[103]  A. Pitsillides,et al.  Characterizing a novel and adjustable noninvasive murine joint loading model. , 2011, Arthritis and rheumatism.

[104]  D. Heinegård,et al.  The role of the cartilage matrix in osteoarthritis , 2011, Nature Reviews Rheumatology.

[105]  J. Cook,et al.  Subchondral bone changes in three different canine models of osteoarthritis. , 2011, Osteoarthritis and cartilage.

[106]  James A. Martin,et al.  Post‐traumatic osteoarthritis: Improved understanding and opportunities for early intervention , 2011, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[107]  T. Wright Biomechanical Factors in Osteoarthritis: The Effects of Joint Instability , 2012, HSS Journal.

[108]  Kosaku Kurata,et al.  Evidence for osteocyte regulation of bone homeostasis through RANKL expression , 2011, Nature Medicine.

[109]  Ning Zuo,et al.  Primary cilia mediate mechanotransduction through control of ATP‐induced Ca2+ signaling in compressed chondrocytes , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[110]  G. Beauchamp,et al.  Relationship between cartilage and subchondral bone lesions in repetitive impact trauma-induced equine osteoarthritis. , 2012, Osteoarthritis and cartilage.

[111]  Hua Zeng,et al.  Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray , 2012, PloS one.

[112]  L. Laslett,et al.  Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial , 2012, Annals of the rheumatic diseases.

[113]  David B. Burr,et al.  Bone remodelling in osteoarthritis , 2012, Nature Reviews Rheumatology.

[114]  L. Sandell Etiology of osteoarthritis: genetics and synovial joint development , 2012, Nature Reviews Rheumatology.

[115]  J. Pelletier,et al.  Future therapeutics for osteoarthritis. , 2012, Bone.

[116]  A. Giaccia,et al.  VEGF‐independent cell‐autonomous functions of HIF‐1α regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival , 2012, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[117]  S. Goldring,et al.  The role of synovitis in osteoarthritis pathogenesis. , 2012, Bone.

[118]  O. Kennedy,et al.  Osteocyte Signaling in Bone , 2012, Current Osteoporosis Reports.

[119]  P. Simkin Consider the Tidemark , 2012, The Journal of Rheumatology.

[120]  O. Kennedy,et al.  Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations. , 2012, Bone.

[121]  F. Reinholt,et al.  Quantitative Proteomic Analysis of Eight Cartilaginous Tissues Reveals Characteristic Differences as well as Similarities between Subgroups* , 2012, The Journal of Biological Chemistry.

[122]  D. Walsh,et al.  Osteochondral alterations in osteoarthritis. , 2012, Bone.

[123]  S. Goldring,et al.  Osteoarthritis: a disease of the joint as an organ. , 2012, Arthritis and rheumatism.

[124]  R. Loeser Aging processes and the development of osteoarthritis , 2013, Current opinion in rheumatology.

[125]  A. Mobasheri The Future of Osteoarthritis Therapeutics: Emerging Biological Therapy , 2013, Current Rheumatology Reports.

[126]  C. L. Murphy,et al.  Hypoxia promotes the production and inhibits the destruction of human articular cartilage. , 2013, Arthritis and rheumatism.

[127]  S. Goldring,et al.  1 – Biology of the Normal Joint , 2013 .

[128]  Mitchell B. Schaffler,et al.  Osteocytes: Master Orchestrators of Bone , 2013, Calcified Tissue International.

[129]  J. Bertrand,et al.  Syndecans in cartilage breakdown and synovial inflammation , 2013, Nature Reviews Rheumatology.

[130]  H. Im,et al.  MMP13 is a critical target gene during the progression of osteoarthritis , 2013, Arthritis Research & Therapy.

[131]  F. Berenbaum,et al.  Homeostatic Mechanisms in Articular Cartilage and Role of Inflammation in Osteoarthritis , 2013, Current Rheumatology Reports.

[132]  M. Lee,et al.  Genome-wide expression profiles of subchondral bone in osteoarthritis , 2013, Arthritis Research & Therapy.

[133]  D. Hunter,et al.  Post-traumatic osteoarthritis: from mouse models to clinical trials , 2013, Nature Reviews Rheumatology.

[134]  J. Pelletier,et al.  New and emerging treatments for osteoarthritis management: will the dream come true with personalized medicine? , 2013, Expert opinion on pharmacotherapy.

[135]  H. Roach,et al.  Regulated Transcription of Human Matrix Metalloproteinase 13 (MMP13) and Interleukin-1β (IL1B) Genes in Chondrocytes Depends on Methylation of Specific Proximal Promoter CpG Sites* , 2013, The Journal of Biological Chemistry.

[136]  A. Mobasheri The Future of Osteoarthritis Therapeutics: Targeted Pharmacological Therapy , 2013, Current Rheumatology Reports.

[137]  B. Dawson,et al.  Proteoglycan 4 Expression Protects Against the Development of Osteoarthritis , 2013, Science Translational Medicine.

[138]  T. Wright,et al.  In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae. , 2013, Arthritis and rheumatism.

[139]  T. Quinn,et al.  Cell and matrix morphology in articular cartilage from adult human knee and ankle joints suggests depth-associated adaptations to biomechanical and anatomical roles. , 2013, Osteoarthritis and cartilage.

[140]  Sarah L Dallas,et al.  The osteocyte: an endocrine cell ... and more. , 2013, Endocrine reviews.

[141]  Jin-Hong Kim,et al.  Regulation of the Catabolic Cascade in Osteoarthritis by the Zinc-ZIP8-MTF1 Axis , 2014, Cell.

[142]  T. Andriacchi,et al.  The Nature of In Vivo Mechanical Signals That Influence Cartilage Health and Progression to Knee Osteoarthritis , 2014, Current Rheumatology Reports.

[143]  Felix Eckstein,et al.  Imaging research results from the Osteoarthritis Initiative (OAI): a review and lessons learned 10 years after start of enrolment , 2014, Annals of the rheumatic diseases.

[144]  Julien Favre,et al.  A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease , 2015, Annals of Biomedical Engineering.

[145]  Lin Xu,et al.  Induction of high temperature requirement A1, a serine protease, by TGF-beta1 in articular chondrocytes of mouse models of OA. , 2014, Histology and histopathology.

[146]  R. Loeser Integrins and chondrocyte–matrix interactions in articular cartilage , 2014, Matrix biology : journal of the International Society for Matrix Biology.

[147]  D. Findlay,et al.  Osteoblast-Chondrocyte Interactions in Osteoarthritis , 2014, Current Osteoporosis Reports.

[148]  O. Kennedy,et al.  Osteocyte apoptosis is required for production of osteoclastogenic signals following bone fatigue in vivo. , 2014, Bone.

[149]  D. Hunter,et al.  The epidemiology of osteoarthritis. , 2014, Best practice & research. Clinical rheumatology.

[150]  G. Hawker,et al.  Osteoarthritis year in review 2014: clinical. , 2014, Osteoarthritis and cartilage.

[151]  F. Guilak,et al.  The structure and function of the pericellular matrix of articular cartilage. , 2014, Matrix biology : journal of the International Society for Matrix Biology.

[152]  R. Ruhlen,et al.  The chondrocyte primary cilium. , 2014, Osteoarthritis and cartilage.

[153]  M. Nevitt,et al.  Biomarkers for osteoarthritis: current position and steps towards further validation. , 2014, Best practice & research. Clinical rheumatology.

[154]  C. Christiansen,et al.  The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments? , 2013, Annals of the rheumatic diseases.

[155]  Ernst B Hunziker,et al.  How best to preserve and reveal the structural intricacies of cartilaginous tissue. , 2014, Matrix biology : journal of the International Society for Matrix Biology.

[156]  R. Terkeltaub,et al.  Emerging regulators of the inflammatory process in osteoarthritis , 2015, Nature Reviews Rheumatology.

[157]  F. Berenbaum,et al.  Emerging targets in osteoarthritis therapy. , 2015, Current opinion in pharmacology.

[158]  E. Losina,et al.  OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis. , 2015, Osteoarthritis and cartilage.

[159]  G. Giles,et al.  Bone marrow lesions can be subtyped into groups with different clinical outcomes using two magnetic resonance imaging (MRI) sequences , 2015, Arthritis Research & Therapy.

[160]  M. Karsdal,et al.  Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials. , 2015, Osteoarthritis and cartilage.

[161]  H. Hwang,et al.  Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis , 2015, International journal of molecular sciences.

[162]  T. H. Haut Donahue,et al.  Assessment of cortical and trabecular bone changes in two models of post‐traumatic osteoarthritis , 2015, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[163]  F. Eckstein,et al.  What Comes First? Multitissue Involvement Leading to Radiographic Osteoarthritis: Magnetic Resonance Imaging–Based Trajectory Analysis Over Four Years in the Osteoarthritis Initiative , 2015, Arthritis & rheumatology.

[164]  P. Torzilli,et al.  A biphasic finite element study on the role of the articular cartilage superficial zone in confined compression. , 2015, Journal of biomechanics.

[165]  F. Berenbaum,et al.  Metabolic stress-induced joint inflammation and osteoarthritis. , 2015, Osteoarthritis and cartilage.

[166]  J. Glowacki,et al.  Influence of osteoarthritis grade on molecular signature of human cartilage , 2016, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[167]  S. Mclure,et al.  Osteoarthritic bone marrow lesions almost exclusively colocate with denuded cartilage: a 3D study using data from the Osteoarthritis Initiative. , 2016, Annals of the Rheumatic Diseases.

[168]  M. Karsdal,et al.  Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria. , 2016, Osteoarthritis and cartilage.

[169]  T. Wright,et al.  Progressive cell‐mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading , 2016, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.