Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy

Abstract

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.

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

“…Histomorphometric analysis revealed that the COL1a1 + SZ was significantly thicker in the injury when compared to the sham controls (Figure C), suggesting an expansion of the fibrocartilaginous condylar cartilage tissue. However, the COL2 + MZ thickness significantly decreased upon disc perforation injury when compared to the sham controls (Figure C), suggesting a loss of mature COL2a1 + chondrocytes, which are critical for cartilage function . Immunohistochemical analysis confirmed a loss of COL2a1 expression in the injured TMJ condyle relative to sham controls (Figure D,E).…”

“…However, the COL2 + MZ thickness significantly decreased upon disc perforation injury when compared to the sham controls ( Figure 3C), suggesting a loss of mature COL2a1 + chondrocytes, which are critical for cartilage function. 1,14 Immunohistochemical analysis confirmed a loss of COL2a1 expression in the injured TMJ condyle relative to sham controls ( Figure 3D,E). Most notably, the injured TMJ condyle demonstrated an expansion of bone-related proteins in the MZ and HZ, including BSP and RUNX2, relative to sham controls, suggesting that the loss of COL2a1 + chondrocytes was coupled with a gain of bone-like cells (Figure 3D,E).…”

“…Hyaline articular cartilage lines joint surfaces in adults and is primarily comprised of chondrocytes that maintain a relatively low rate of metabolic turnover under hypoxic conditions. 1,2 Chondrocytes are embedded within an avascular, extracellular matrix (ECM) enriched in proteoglycans and non-collagenous proteins that are fixed in a complex network of collagens. [3][4][5] The ECM provides diverse functions in articular cartilage, including providing biomechanical strength, anchorage for chondrocytes, and regulation of intercellular and ECM communication.…”

“…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).…”

Bioreactor‐manufactured cartilage grafts repair acute and chronic osteochondral defects in large animal studies

“…As reported in the literature, it is possible that the inflammatory environment in the chronic defect has facilitated the conversion of cartilage into bone. 17 The results of the chronic model are quite impressive considering the mechanical loading and inflammatory conditions that the grafts were subjected to. Since sheep were not immobilized after surgery, the animals could walk freely post-operatively.…”