Autophagy, a mechanism of organelle recycling that promotes cell survival, has been previously implicated in osteoarthritis (OA). One of the proteins fundamental to this process, autophagy protein 5 (Atg5), has now been shown to be protective against late-onset OA in a new study in mice.
“Despite numerous suggestions of a connection between autophagy and OA, direct physiological evidence [was] missing,” explains Andrei Chagin, corresponding author of the study. To evaluate the importance of autophagy in the development of OA, Chagin and colleagues studied the onset of age-related and trauma-induced OA in mice lacking Atg5 specifically in chondrocytes (Atg5cKO mice).
Evidence of fibrillation and reduced proteoglycan deposition in articular cartilage was first observed in male Atg5cKO mice at the age of 6 months, a time when no abnormalities were detected in control or female Atg5cKO mice. At 1 year of age, Atg5cKO male mice showed extensive fibrillation, further reduction in proteoglycan deposition and increased collagenase-3 expression in joints compared with controls. Cartilage degradation was also observed in age-matched female Atg5cKO mice, and OARSI histopathology scores were higher in male and female Atg5cKO mice than in gender-matched controls (P = 0.002 and P = 0.006, respectively).
The researchers also found evidence of increased chondrocyte apoptosis in Atg5cKO mice compared with controls, as well as a higher number of chondrocytes positive for cleaved caspase-3 and caspase-9, two apoptosis markers. Intriguingly, none of the differences reported between Atg5cKO mice and controls in the onset of age-related OA were observed in a model of trauma-induced OA in which mice were subjected to partial medial meniscectomy.
“These data are in line with the general view of autophagy as a protective mechanism which facilitates cell survival in unfavourable conditions,” concludes Chagin. “New questions now require attention, including how autophagy protective mechanisms work and whether autophagy has a role in other cells of the joint.”
References
Bouderlique, T. et al. Targeted deletion of Atg5 in chondrocytes promotes age-related osteoarthritis. Ann. Rheum. Dis. doi: 10.1136/annrheumdis-2015-207742
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Duarte, J. Autophagy prevents age-related OA. Nat Rev Rheumatol 11, 683 (2015). https://doi.org/10.1038/nrrheum.2015.145
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DOI: https://doi.org/10.1038/nrrheum.2015.145
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