The dual role of autophagy in chondrocyte responses in the pathogenesis of articular cartilage degeneration in osteoarthritis

Abstract

The present study aimed to analyze the responses to autophagy in osteoarthritis (OA) and aging chondrocytes in order to elucidate the role of autophagy in the pathogenesis of OA. We used multiple assays to confirm that autophagic activity was downregulated in chondrocytes of aged articular cartilage. Surprisingly, we found that the expression of autophagy-related proteins was not decreased in the tissues of patients with OA. We also observed that rapamycin-induced autophagy prevented the accumulation of subdiploid cells in young chondrocytes, while it induced cell death by autophagy in OA chondrocytes. Our results demonstrate that autophagic activity decreases with aging, and may be responsible for the cytoprotective effects in young cartilage. However, we found that autophagic activity in patients with OA was higher than in the aging group, and reported autophagic cell death in OA chondrocytes. These results suggest that autophagy plays both a cytoprotective and death-promoting role in the pathogenesis of OA.

Autophagy Activation by Rapamycin Before Hypoxia-Reoxygenation Reduces Endoplasmic Reticulum Stress in Alveolar Epithelial Cells

“…Although our study may preliminarily imply the beneficial effects for reduction of the UPR response and alleviation of H/R induced ER stress by the use of autophagy agonist Rap before H/R, more attention should be paid that there may be dual functions of up-regulation of autophagy to both protect and cause death of cells indicated by some studies [45,46]. We believe the function of autophagy in H/R depends on the exposure conditions (such as time) and might, likewise, differ between cell or disease types.…”

AntimiR-30b Inhibits TNF-α Mediated Apoptosis and Attenuated Cartilage Degradation through Enhancing Autophagy

“…Aging is an important risk factor for the development of OA and is associated with the progressive accumulation of damaged macromolecules and organelles in somatic cells [27], potentially mediated by downregulation of the autophagic disposal of such damaged cellular components [28]. Autophagy-related proteins unc-51-like autophagy activating kinase 1 (ULK1), Beclin1 and microtubule-associated protein 1A/1B-light chain 3 (LC3) are reported to be expressed at high levels in healthy human cartilage [25,29,30], however, their expression decreases during OA [25,26]. Mechanistic target of rapamycin complex 1 (mTORC1) intracellular signalling pathway is an autophagic regulator that when inhibited activates the process of autophagy [31].…”

Responses and adaptations of intervertebral disc cells to microenvironmental stress: a possible central role of autophagy in the adaptive mechanism

“…However, autophagy plays dichotomous roles in several diseases. Excessive autophagy might exacerbate the death of chondrocytes and synovial fibroblasts in rheumatoid arthritis (20,21). ''Autophagic cell death'', which refers to cell deathassociated autophagy, is extensively used in studies about autophagy, though direct and precise evidence demonstrating that autophagy leads to the execution of cell death remains limited (22).…”