Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis—structure, chaos and senescence

Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis—structure, chaos and senescence

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ABSTRACT The extracellular matrix of articular cartilage is the primary target of osteoarthritic cartilage degradation. However, cartilage cells have a pivotal role during osteoarthritis, as


they are mainly responsible for the anabolic–catabolic balance required for matrix maintenance and tissue function. In addition to the severe changes in the extracellular matrix, the cells


also display abnormalities during osteoarthritic cartilage degeneration, such as inappropriate activation of anabolic and catabolic activities, and alterations in cell number through


processes like proliferation and (apoptotic) cell death. The cells are exposed to additional stimuli such as nonphysiologic loading conditions and byproducts of matrix destruction, as well


as abnormal levels of cytokines and growth factors. This exposure can lead to a structured cellular response pattern that may be either beneficial or detrimental to the cartilage tissue.


Potentially even more problematic for preserving tissue homeostasis, neighboring osteoarthritic chondrocytes display strong heterogeneity in their phenotype, gene expression patterns, and


cellular responses. As the disease progresses, osteoarthritic chondrocytes can no longer maintain tissue integrity. Evidence suggests that cell aging is important in the pathogenesis of


osteoarthritis. Thus, anti-aging strategies might complement existing therapeutic targets related to anabolism, catabolism, inflammation, and apoptosis—processes that are integral to the


pathogenesis of osteoarthritis. KEY POINTS * Osteoarthritic chondrocytes are exposed to many external factors and respond with a large spectrum of phenotypic and behavioral changes


(anabolic, catabolic, proliferative, apoptotic, etc.) * Many of the biological changes occurring in osteoarthritic chondrocytes mimic the differentiation pattern that occurs during fetal


skeletogenesis * The extraordinarily pleomorphic behavior of osteoarthritic chondrocytes suggests an unstructured/stochastic reaction pattern * Damage to the genome induced by oxidative


damage and/or reactive oxygen species may be responsible for some of the so far unexplained heterogenous gene transcription patterns * Premature aging of chondrocytes might be important in


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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS CROSS-TALK OF INFLAMMATION AND CELLULAR SENESCENCE: A NEW INSIGHT INTO THE OCCURRENCE AND PROGRESSION OF OSTEOARTHRITIS


Article Open access 03 December 2024 IΚB-Ζ SIGNALING PROMOTES CHONDROCYTE INFLAMMATORY PHENOTYPE, SENESCENCE, AND EROSIVE JOINT PATHOLOGY Article Open access 11 February 2022 MECHANISMS AND


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Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by the Deutsche Forschungsgemeinschaft (DFG Ai 20/7–1). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS


* J Haag is a Senior Research Fellow and PM Gebhard is a PhD Student. A McAlinden is an Assistant Professor in the Department of Orthopedic Surgery, T Aigner is a Senior Staff Pathologist


and Deputy Director of the Institute of Pathology, University of Leipzig, Germany, where S Söder is a Clinical Research Fellow, Washington University School of Medicine, St Louis, MO, USA.,


Thomas Aigner, Stefan Söder, Pia M Gebhard, Audrey McAlinden & Jochen Haag Authors * Thomas Aigner View author publications You can also search for this author inPubMed Google Scholar *


Stefan Söder View author publications You can also search for this author inPubMed Google Scholar * Pia M Gebhard View author publications You can also search for this author inPubMed Google


Scholar * Audrey McAlinden View author publications You can also search for this author inPubMed Google Scholar * Jochen Haag View author publications You can also search for this author


inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Thomas Aigner. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RIGHTS AND


PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Aigner, T., Söder, S., Gebhard, P. _et al._ Mechanisms of Disease: role of chondrocytes in the pathogenesis of


osteoarthritis—structure, chaos and senescence. _Nat Rev Rheumatol_ 3, 391–399 (2007). https://doi.org/10.1038/ncprheum0534 Download citation * Received: 11 August 2006 * Accepted: 01 May


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