Kynurenic acid promotes osteogenesis via the Wnt/β-catenin signaling

The role of kynurenic acid (KynA) in neurological and mental diseases has been widely studied. Emerging studies disclosed that KynA has a protective effect on tissues including heart, kidney, and retina. However, the role of KynA in osteoporosis has not been reported so far. To elucidate the role of KynA in age-related osteoporosis, both control and osteoporosis mice were administrated KynA for three consecutive months, and micro-computed tomography (μCT) analysis was then performed. In addition, primary bone marrow mesenchymal stem cells (BMSCs) were isolated for osteogenic differentiation induction and treated with KynA in vitro. Our data suggested that KynA administration rescued age-related bone loss in vivo, and KynA treatment promotes BMSC osteogenic differentiation in vitro. Moreover, KynA activated the Wnt/β-catenin signaling during BMSC osteogenic differentiation. Wnt inhibitor MSAB inhibited KynA-induced osteogenic differentiation. Further data demonstrated that KynA exerted its effect on BMSC osteogenic differentiation and Wnt/β-catenin signaling activation via G protein-coupled receptor 35 (GPR35). In conclusion, the protective effect of KynA on age-related osteoporosis was disclosed. Additionally, the promoting effect of KynA on osteoblastic differentiation via Wnt/β-catenin signaling was verified and the effect dependent on GPR35. These data suggest that KynA administration potentially contributes to the treatment of age-related osteoporosis.