Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

Abstract

Osteoarthritis (OA) is a joint pathology characterized by progressive cartilage degradation. Medical care is mainly based on alleviating pain symptoms. Compelling studies report the presence of empty lacunae and hypocellularity in cartilage with aging and OA progression, suggesting that chondrocyte cell death occurs and participates to OA development. However, the relative contribution of apoptosis per se in OA pathogenesis appears complex to evaluate. Indeed, depending on technical approaches, OA stages, cartilage layers, animal models, as well as in vivo or in vitro experiments, the percentage of apoptosis and cell death types can vary. Apoptosis, chondroptosis, necrosis, and autophagic cell death are described in this review. The question of cell death causality in OA progression is also addressed, as well as the molecular pathways leading to cell death in response to the following inducers: Fas, Interleukin-1β (IL-1β), Tumor Necrosis factor-α (TNF-α), leptin, nitric oxide (NO) donors, and mechanical stresses. Furthermore, the protective role of autophagy in chondrocytes is highlighted, as well as its decline during OA progression, enhancing chondrocyte cell death; the transition being mainly controlled by HIF-1α/HIF-2α imbalance. Finally, we have considered whether interfering in chondrocyte apoptosis or promoting autophagy could constitute therapeutic strategies to impede OA progression.

Apitherapy for Osteoarthritis: Perspectives from Basic Research

“…Although the role of the inflammatory process in the development and evolution of OA was initially underestimated, we now understand the importance of the inflammation in OA pathogenesis. Nitric oxide and ROS have been shown to modify the effects of TGF-B and expression of NF-κB-dependent genes [21]. The alteration in the expression and functioning of TGF-B is related to the development of OA [22].…”

Chondroprotective Effects of Ginsenoside Rg1 in Human Osteoarthritis Chondrocytes and a Rat Model of Anterior Cruciate Ligament Transection

“…Interleukin (IL)-1β, a major pro-inflammatory cytokine produced by chondrocytes and synovial cells, contributes to increased chondrocyte apoptosis [1,2,3], along with the synthesis of other inflammatory mediators, including matrix metalloproteinase (MMP), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE 2 ). These inflammatory mediators ultimately inhibit type II collagen and aggrecan synthesis, increase extracellular matrix (ECM) degradation, and cause articular cartilage damage [4,5,6,7].…”

BST106 Protects against Cartilage Damage by Inhibition of Apoptosis and Enhancement of Autophagy in Osteoarthritic Rats

“…An imbalance between anabolism and catabolism of extracellular matrix (ECM) components is the central feature in cartilage destruction. 1) The massive loss of ECM results from cleavage of type II collagen and aggrecan, a predominant proteoglycan, and the consequent release of GAG which is covalently linked to core proteins to form proteoglycans. 28) MMPs, a family of proteolytic enzymes, play pivotal role in the degradation of ECM and mediate cartilage destruction and joint erosion.…”

“…Previous studies demonstrated that cartilage destruction in OA results from inflammation-induced matrix metalloproteinase (MMP) activation. 1) Furthermore, compelling studies reported that chondrocyte cell death such as apoptosis and necrosis participates in OA development, which appears to be complex. 2) Despite extensive studies on cartilage loss and degradation in OA, the exact pathologic mechanisms are not fully understood.…”

“…1) Furthermore, compelling studies reported that chondrocyte cell death such as apoptosis and necrosis participates in OA development, which appears to be complex. 2) Despite extensive studies on cartilage loss and degradation in OA, the exact pathologic mechanisms are not fully understood. The main symptoms of OA include pain, inflammation, stiffness, and loss of mobility in joints.…”