Achyranthes bidentata extract protects chondrocytes functions through suppressing glycolysis and apoptosis via MAPK/AKT signaling axis.

Osteoarthritis (OA) is considered to be a joint-associated disorder and one of leading reasons for disability, however, potential mechanism has never been clarified. The purpose of this research was to evaluate protective-effects of Achyranthes Bidentata extracts (ABE) on chondrocytes function in osteoarthritis. We performed a systematic investigation of transcriptional and proteomic landscapes to identify the underlying mechanisms behind effects of ABE on chondrocytic functions. OA animal models were generated in the present research. Chondrocytes were isolated and cultured, and then prepared for GeneChip analysis. Two-dimensional gel electrophoresis and LC-MS/MS analysis were conducted to analyze samples. Quantitative real-time PCR (qRT-PCR) and western blotting were used to evaluate expression of protein kinase B (AKT), beta-tubulin and beta-action. Apoptosis and glycolysis pathway were significantly compromised in chondrocytes with ABE stimulation as revealed by both transcriptional and proteomic data. Consistently, ABE suppressed chondrocytes apoptosis and glycolytic activity in vitro through modulating multiple genes, such as Plk2, Casp1/12 and Cers1 as well as Pkm2, Eno1/3 and Pgk2. Mechanically, ABE activated MAPK signaling pathway and suppressed AKT signaling pathway, therefore, reducing the glycolysis to provide survival benefits. We extended our analysis by verifying insulin-like growth factor 1 (IGF-1) and MAP kinase 1 (MEK1) in chondrocytes function. Depletion of either IGF-1 or MEK1 impaired AKT expression and phosphorylation, leading to the enhanced chondrocyte apoptosis and reduced cell proliferation. In conclusion, our study provided systematic view and molecular basis for ABE to serve as potential intervention of OA via suppressing AKT signaling.