Diabetes-accelerated experimental osteoarthritis is prevented by autophagy activation

Osteoarthritis Cartilage. 2016 Dec;24(12):2116-2125. doi: 10.1016/j.joca.2016.06.019. Epub 2016 Jul 5.


Objective: Type 2 Diabetes (T2D) is a risk factor for osteoarthritis (OA). Autophagy, an essential homeostasis mechanism in articular cartilage, is defective in T2D and OA. However, how T2D may influence OA progression is still unknown. We aimed to determine how diabetes affects cartilage integrity and whether pharmacological activation of autophagy has efficacy in diabetic mice (db/db mice) with OA.

Design: Experimental OA was performed in the right knee of 9 weeks-old C57Bl/6J male mice (Lean group, N = 8) and of 9 weeks-old B6.BKS (D)-Leprdb male mice (db/db group, N = 16) by transection of medial meniscotibial and medial collateral ligaments. Left knee was employed as control knee. Rapamycin (2 mg/kg weight/day) or Vehicle (dimethyl sulfoxide) were administered intraperitoneally three times a week for 10 weeks. Histopathology of articular cartilage and synovium was evaluated by using semiquantitative scoring and synovitis grading systems, respectively. Immunohistochemistry was employed to evaluate the effect of diabetes and Rapamycin on cartilage integrity and OA biomarkers.

Results: Cartilage damage was increased in db/db mice compared to Lean mice after experimental OA, while no differences are observed in the control knee. Cartilage damage and synovium inflammation were reduced by Rapamycin treatment of OA-db/db mice. This protection was accompanied with a decrease in MMP-13 expression and decreased interleukin 12 (IL-12) levels. Furthermore, autophagy was increased and cartilage cellularity was maintained, suggesting that mammalian target of rapamycin (mTOR) targeting prevents joint physical harm.

Conclusion: Our findings indicate that diabetic mice exhibit increased joint damage after experimental OA, and that autophagy activation might be an effective therapy for diabetes-accelerated OA.

Keywords: Autophagy; Cartilage; Diabetes; Osteoarthritis; Synovium; mTOR.

MeSH terms

  • Animals
  • Autophagy*
  • Cartilage, Articular
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 2
  • Male
  • Mice
  • Osteoarthritis