The Role of Chondrocyte Morphology and Volume in Controlling Phenotype—Implications for Osteoarthritis, Cartilage Repair, and Cartilage Engineering

Abstract

Purpose of Review Articular chondrocytes are exclusively responsible for the turnover of the extracellular matrix (ECM) of hyaline cartilage. However, chondrocytes are phenotypically unstable and, if they de-differentiate into hypertrophic or fibroblastic forms, will produce a defective and weak matrix. Chondrocyte volume and morphology exert a strong influence over phenotype and a full appreciation of the factors controlling chondrocyte phenotype stability is central to understanding (a) the mechanisms underlying the cartilage failure in osteoarthritis (OA), (b) the rationale for hyaline cartilage repair, and (c) the strategies for improving the engineering of resilient cartilage. The focus of this review is on the factors involved in, and the importance of regulating, chondrocyte morphology and volume as key controllers of chondrocyte phenotype. Recent Findings The visualisation of fluorescently-labelled in situ chondrocytes within non-degenerate and mildly degenerate cartilage, by confocal scanning laser microscopy (CLSM) and imaging software, has identified the marked heterogeneity of chondrocyte volume and morphology. The presence of chondrocytes with cytoplasmic processes, increased volume, and clustering suggests important early changes to their phenotype. Results from experiments more closely aligned to the normal physico-chemical environment of in situ chondrocytes are emphasising the importance of understanding the factors controlling chondrocyte morphology and volume that ultimately affect phenotype. Summary An appreciation of the importance of chondrocyte volume and morphology for controlling the chondrocyte phenotype is advancing at a rapid pace and holds particular promise for developing strategies for protecting the chondrocytes against deleterious changes and thereby maintaining healthy and resilient cartilage.

Evidence of vasculature and chondrocyte to osteoblast transdifferentiation in craniofacial synovial joints: Implications for osteoarthritis diagnosis and therapy

“…4,[9][10][11] Given that it is well established that cartilage is avascular, 12,13 the current OA pathological paradigm supports the idea that chondrocyte phenotypic stability plays a pivotal role in maintaining the delicate balance of tissue and ECM homeostasis. 1,6,7,14,15 During OA pathogenesis, the functional demands of the articular cartilage surpass the chondrocytes' ability to repair the ECM, leading to changes in chondrocyte phenotype and cartilage degradation. 4,10,16 While these concepts are well-established for hyaline articular cartilages lining the appendicular skeleton, little is known about chondrocyte stability in the fibrocartilage craniofacial synovial joint called the temporomandibular joint (TMJ).…”

Acteoside counteracts interleukin-1β-induced catabolic processes through the modulation of mitogen-activated protein kinases and the NFκB cellular signaling pathway

“…Especially, the extracellular matrix (ECM) of articular cartilage is composed mainly of type II collagen and proteoglycans that are synthesized and regulated by specialized cells called as chondrocytes. The homeostasis of articular cartilage is precisely balanced between anabolism (synthesis of ECM) and catabolism (degeneration of ECM) in synovial joints [18]. Generally, catabolic factors such as proin ammatory cytokines and in ammatory mediators induce the progressive degeneration of articular cartilage through the expression of cartilage degrading enzymes such as matrix metalloproteinase (MMPs) and metalloproteinase with thrombospondin motifs (ADAMTs) from chondrocytes [18].…”

“…The homeostasis of articular cartilage is precisely balanced between anabolism (synthesis of ECM) and catabolism (degeneration of ECM) in synovial joints [18]. Generally, catabolic factors such as proin ammatory cytokines and in ammatory mediators induce the progressive degeneration of articular cartilage through the expression of cartilage degrading enzymes such as matrix metalloproteinase (MMPs) and metalloproteinase with thrombospondin motifs (ADAMTs) from chondrocytes [18]. Hence, recent biochemical strategies to prevent or attenuate the progressive degeneration of articular cartilage have targeted the suppression of cartilage degrading enzymes, pro-in ammatory cytokines, and in ammatory mediators based on the long-term biological safeties in synovial joints [19,20].…”

Abnormal craniofacial and spinal bone development withcol2a1a depletion in a zebrafish model of CHARGE syndrome

“…(72)(73)(74) The hypertrophic morphology of the chondrocytes seen in our study may indicate signs of a weakened matrix, as well as altered matrix composition and may contribute to an increased risk in osteoporosis. (75,76) How this regulatory defect may influence other cartilage/skeletal regions such as the craniofacial cartilage remains to be investigated.…”