Active Vitamin D activates chondrocyte autophagy to reduce osteoarthritis via mediating the AMPK/mTOR signaling pathway.

Abstract

Osteoarthritis (OA) is a common joint degenerative disease. Vitamin D (VD) is essential for bone function in human body. We hypothesized that active VD may play key functions in OA treatment. Low level of serum 25-hydroxyvitamin D (25(OH)D) was found in OA patients, and the serum VD level might be supportive for OA diagnosis. OA mouse models were established. HE and SafraninO/Fast Green staining suggested that active VD reduced OA symptoms in mice. VD treatment elevated p-AMPK/AMPK and decreased p-mTOR/mTOR, and it increased LC3II/LC3I, increased the protein level of Beclin-1, but decreased p62 according to Western blot analysis. Besides, VD reduced the contents of tumor necrosis factor-α and interleukin-6 both in cartilage tissues and in chondrocytes. Meanwhile, AMPK inhibitor Compound C and autophagy inhibitor 3-methyladenine (3-MA) reversed these changes following VD treatment. In addition, mRFP-GFP-LC3 transfection identified that active VD led to autophagosome aggregation in OA chondrocytes. 3-MA inhibited cell autophagy and promoted OA inflammation. This study provided evidence that active VD might activate chondrocyte autophagy to reduce OA inflammation via activating the AMPK/mTOR signaling pathway. Active OA treatment might serve as a novel therapeutic option for OA treatment.