Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis.
TLDR
Understanding how the chondrocytes in adult human cartilage undergo phenotypic modulation and promote matrix destruction and abnormal repair in OA may to lead to identification of critical targets for therapy to block cartilage damage and promote effective cartilage repair.Abstract:
Chondrogenesis occurs as a result of mesenchymal cell condensation and chondroprogenitor cell differentiation. Following chondrogenesis, the chondrocytes remain as resting cells to form the articular cartilage or undergo proliferation, terminal differentiation to chondrocyte hypertrophy, and apoptosis in a process termed endochondral ossification, whereby the hypertrophic cartilage is replaced by bone. Human adult articular cartilage is a complex tissue of matrix proteins that varies from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue-engineering strategies is the inability of the resident chondrocytes to lay down a new matrix with the same properties as it had when it was formed during development. Thus, understanding and comparing the mechanisms of cartilage remodeling during development, osteoarthritis (OA), and aging may lead to more effective strategies for preventing cartilage damage and promoting repair. The pivotal proteinase that marks OA progression is matrix metalloproteinase 13 (MMP-13), the major type II collagen-degrading collagenase, which is regulated by both stress and inflammatory signals. We and other investigators have found that there are common mediators of these processes in human OA cartilage. We also observe temporal and spatial expression of these mediators in early through late stages of OA in mouse models and are analyzing the consequences of knockout or transgenic overexpression of critical genes. Since the chondrocytes in adult human cartilage are normally quiescent and maintain the matrix in a low turnover state, understanding how they undergo phenotypic modulation and promote matrix destruction and abnormal repair in OA may to lead to identification of critical targets for therapy to block cartilage damage and promote effective cartilage repair.read more
Citations
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Synovitis in osteoarthritis: current understanding with therapeutic implications.
TL;DR: Current knowledge on the prevalence of synovial inflammation in OA and its role in symptoms and structural progression is reviewed, and lessons learnt from targeting synovitis therapeutically are explored.
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Aging and osteoarthritis: Central role of the extracellular matrix
TL;DR: This review will systematically analyze cellular and structural changes taking place in the articular cartilage and bone in the pathogenesis of OA which are linked to aging and place a particular emphasis on age-related changes in the phenotype of theArticular chondrocytes.
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Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies.
TL;DR: The premise for the presence of crosstalk in bone-cartilage interface as well as the current knowledge of the major signalling pathways and molecular interactions that regulate OA progression are summarised.
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Lubrication of Articular Cartilage
TL;DR: Such lubrication in the light of very recent advances in the understanding of boundary effects in aqueous media based on the paradigms of hydration lubrication and of the synergism between different molecular components of the synovial joints (namely hyaluronan, lubricin, and phospholipids) in enabling this lubrication are discussed.
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Chondrocyte dedifferentiation and osteoarthritis (OA)
Edith Charlier,Céline Deroyer,Federica Ciregia,Olivier Malaise,Sophie Neuville,Zelda Plener,Michel Malaise,Dominique de Seny +7 more
TL;DR: Molecular knowledge underlying dedifferentiation process is presented, connections between dedifferentiated-like and OA are emphasized and therapeutic strategies aiming at the maintenance of chondrogenic phenotype are considered.
References
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