Department of Orthopedics, The First Hospital of Yulin, No. 93, Yu Xi Street, Yulin, 719000, Shaanxi, People's Republic of China.
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
In Vitro Cell Dev Biol Anim. 2023 May;59(5):356-365. doi: 10.1007/s11626-023-00774-2. Epub 2023 Jun 8.
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.
犬尿酸（KynA）在神经和精神疾病中的作用已得到广泛研究。新出现的研究表明，KynA 对包括心脏、肾脏和视网膜在内的组织具有保护作用。然而，迄今为止，KynA 在骨质疏松症中的作用尚未报道。为了阐明 KynA 在与年龄相关的骨质疏松症中的作用，我们对对照组和骨质疏松症小鼠连续三个月给予 KynA 治疗，然后进行微计算机断层扫描（μCT）分析。此外，我们还分离了原代骨髓间充质干细胞（BMSCs）进行成骨分化诱导，并在体外用 KynA 处理。我们的数据表明，KynA 给药可挽救体内与年龄相关的骨丢失，KynA 处理可促进体外 BMSC 成骨分化。此外，KynA 在 BMSC 成骨分化过程中激活了 Wnt/β-catenin 信号通路。Wnt 抑制剂 MSAB 抑制了 KynA 诱导的成骨分化。进一步的数据表明，KynA 通过 G 蛋白偶联受体 35（GPR35）发挥其对 BMSC 成骨分化和 Wnt/β-catenin 信号通路激活的作用。总之，我们揭示了 KynA 对与年龄相关的骨质疏松症的保护作用。此外，我们验证了 KynA 通过 Wnt/β-catenin 信号通路促进成骨细胞分化的作用，并证明这种作用依赖于 GPR35。这些数据表明，KynA 给药可能有助于治疗与年龄相关的骨质疏松症。
