N-acetyl-L-cysteine enhances the osteogenic differentiation and inhibits the adipogenic differentiation through up regulation of Wnt 5a and down regulation of PPARG in bone marrow stromal cells.

Nowadays, the treatment of osteoporosis is still a great challenge in the medical field. The combination of enhancement of osteogenesis and the inhibition of adipogenesis of bone marrow stromal cells (BMSCs) is considered an efficient therapeutic strategy for the treatment of osteoporosis. In the present study, we investigated the effects of N-acetyl-L-cysteine (NAC) on the proliferation, osteogenesis and adipogenesis of BMSCs. NAC treatment enhanced the alkaline phosphatase activity, mineral deposition and mRNA expression levels of osteogenesis markers collagen I, osteopontin, and signal pathway related protein Wingless-type family member 5a in addition to Wingless-type family member 3a during osteogenic induction, and inhibited the accumulation of lipid droplets and the expression levels of lipoprotein lipase, fatty acid binding protein 4 and peroxisome proliferator-activated receptor gamma mRNA during adipogenic induction. Meanwhile, NAC had the same effects as enhancing mineral deposition in regular culture condition. In addition, cell proliferation was also promoted by NAC treatment in regular culture condition. These results suggested that NAC may enhance osteogenic differentiation and inhibit adipogenic differentiation of BMSCs, which is at least partially mediated by up regulating Wnt 5a and down regulating PPARG. Taking into account the extensive protective effects of NAC and that the maintenance of BMSCs number is an important factor in osteoporosis prevention and treatment, these observations suggested that NAC is a promising potential drug for the prevention and treatment of osteoporosis and its associated diseases.