Chrysophanic acid shifts the differentiation tendency of BMSCs to prevent alcohol-induced osteonecrosis of the femoral head

Abstract

Objectives: Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. Materials and Methods: The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. Results: In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. Conclusions: We demonstrated that CPA ameliorated alcohol-induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.