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-1 (IL-1 ), Tumor Necrosis factor- (TNF- ), 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-1 /HIF-2 imbalance. Finally, we have
considered whether interfering in chondrocyte apoptosis or promoting autophagy could constitute
therapeutic strategies to impede OA progression.