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Review
. 2016 Dec 20;17(12):2146.
doi: 10.3390/ijms17122146.

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

Edith Charlier  1 , Biserka Relic  2 , Céline Deroyer  3 , Olivier Malaise  4 , Sophie Neuville  5 , Julie Collée  6 , Michel G Malaise  7 , Dominique De Seny  8
Affiliations
Review

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

Edith Charlier et al. Int J Mol Sci. .

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 VSports手机版. 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. .

Keywords: apoptosis; autophagy; chondrocytes; chondroptosis; necrosis; osteoarthritis V体育安卓版. .

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Molecular mechanisms of chondrocyte cell death. Chondrocyte death can be mediated by mitochondria dysfunction, Fas/FasL engagement, as well as by Nitric Oxide (NO) and Reactive Oxygen Species (ROS) production. p38 is often emphasized as a mediator of chondrocyte cell death, using various stimuli. Silencing of type II collagen or α1 integrin can cause chondrocyte cell death. Numerous miRNAs are IL-1β-responsive and play a role in osteoarthritis (OA) development and chondrocyte cell death. * The current view is that the trigger of autophagy in chondroctyes aims to avoid cell death, especially in the early stages of OA. However, the dotted arrow (depicted on the schema) emphasizes that excess autophagy can also lead to cell death.
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