Glucosamine regulates autophagy in vitro and in vivo

Abstract

ObjectiveTo determine whether glucosamine (GlcN), a dietary supplement that is safe and beneficial in cellular and animal models of joint health, can activate autophagy, an essential cellular homeostasis mechanism that was found deficient in ageing and osteoarthritis (OA) cartilage.MethodsChondrocytes from normal human joints were treated with GlcN‐HCl (1 or 10 mM). Autophagy activation and mTOR signaling was determined by Western Blotting. Reporter mice with green fluorescent protein fused to the autophagy marker LC3 (GFP‐LC3 mice) were treated with GlcN‐HCl (250 mg/kg weight/day) for 7 days. Autophagy activation was analyzed by confocal microscopy and immunohistochemistry.ResultsGlcN treatment of chondrocytes induced autophagy by increasing LC3‐II expression, a main marker of autophagy. This was accompanied by inhibition of ribosomal protein S6 phosphorylation (prbS6), a target of mTOR. In GFP‐LC3 mice, gavage administration of GlcN led to a marked activation of autophagy in liver. In articular cartilage and menisci, there was a decrease in prbS6 expression.ConclusionsGlcN modulates several components of the autophagy pathway in vitro and in vivo. These findings suggest that GlcN is an effective autophagy activator and motivate future studies on its efficacy in modifying aging‐related cellular changes and supporting joint health.Support: Funding provided by Cargill, Inc.