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Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy
Author(s) -
Singh Purva,
Marcu Kenneth B.,
Goldring Mary B.,
Otero Miguel
Publication year - 2019
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13930
Subject(s) - aggrecanase , osteoarthritis , muscle hypertrophy , chondrocyte , cartilage , phenotype , microbiology and biotechnology , anabolism , medicine , biology , endocrinology , pathology , articular cartilage , anatomy , genetics , alternative medicine , gene
Articular chondrocytes are quiescent, fully differentiated cells responsible for the homeostasis of adult articular cartilage by maintaining cellular survival functions and the fine‐tuned balance between anabolic and catabolic functions. This balance requires phenotypic stability that is lost in osteoarthritis (OA), a disease that affects and involves all joint tissues and especially impacts articular cartilage structural integrity. In OA, articular chondrocytes respond to the accumulation of injurious biochemical and biomechanical insults by shifting toward a degradative and hypertrophy‐like state, involving abnormal matrix production and increased aggrecanase and collagenase activities. Hypertrophy is a necessary, transient developmental stage in growth plate chondrocytes that culminates in bone formation; in OA, however, chondrocyte hypertrophy is catastrophic and it is believed to initiate and perpetuate a cascade of events that ultimately result in permanent cartilage damage. Emphasizing changes in DNA methylation status and alterations in NF‐κB signaling in OA, this review summarizes the data from the literature highlighting the loss of phenotypic stability and the hypertrophic differentiation of OA chondrocytes as central contributing factors to OA pathogenesis.