Trifolirhizin protects ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation and bone resorption
Zihong Lin,
Zhigao Zhou,
Jiajie Ye,
Jinfu Wei,
Shaozhe Chen,
Wenyun Zhou,
Yonghao Bi,
Zibin Zhou,
Gang Xie,
Guixin Yuan,
Guanfeng Yao
Affiliations
Zihong Lin
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Department of Shantou Central Hospital, Shantou, Guangdong, China
Zhigao Zhou
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Shantou University Medical College, Shantou, Guangdong, China
Jiajie Ye
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Shantou University Medical College, Shantou, Guangdong, China
Jinfu Wei
Shantou University Medical College, Shantou, Guangdong, China; Department of Orthopedics, The Sixth Affiliated Hospital,School of Medicine, South China University of Technology, Foshan, Guangdong, China
Shaozhe Chen
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Shantou University Medical College, Shantou, Guangdong, China
Wenyun Zhou
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Shantou University Medical College, Shantou, Guangdong, China
Yonghao Bi
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Shantou University Medical College, Shantou, Guangdong, China
Zibin Zhou
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Shantou University Medical College, Shantou, Guangdong, China
Gang Xie
Shantou University Medical College, Shantou, Guangdong, China
Guixin Yuan
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Corresponding author. Department of Orthopedics, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, Guangdong, China.
Guanfeng Yao
Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; Corresponding author. Department of Orthopedics, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515000, Guangdong, China.
Background: Osteoporosis is a debilitating condition characterized by reduced bone density and microstructure, leading to increased susceptibility to fractures and increased mortality, particularly among older individuals. Despite the availability of drugs for osteoporosis treatment, the need for targeted and innovative agents with fewer adverse effects persists. Trifolirhizin, a natural pterostalin derived from the root of Sophora flavescens, has been previously studied for its effects on certain anticancer and antiinflammatory. The impact of trifolirhizin on the formation and function of osteoclasts remain unclear. Purpose: Herein, the possible roles of trifolirhizin the formation and function of osteoclasts and the underlying mechanism were explored. Methods: Bone marrow-derived macrophages (BMMs) were employed to evaluate the roles of trifolirhizin on steoclastogenesis, bone absorption and the underlying mechanism in vitro. Bone loss model was established by ovariectomy(OVX) in mice in vivo. Results: Trifolirhizin repressed osteoclastogenesis, bone resorption induced by receptor activator of nuclear factor kappa B ligand (RANKL) in vitro. Mechanistically, trifolirhizin inhibits RANKL-induced MAPK signal transduction and NFATc1 expression. Moreover, trifolirhizin inhibited osteoclast marker gene expression, including NFATc1, CTSK, MMP9, DC-STAMP, ACP5, and V-ATPase-D2. Additionally, trifolirhizin was found to protect against ovariectomy(OVX)-induced bone loss in mice. Conclusion: Trifolirhizin can effectively inhibit osteoclast production and bone resorption activity. The results of our study provide evidence for trifolirhizin as a potential drug for the prevention and treatment of osteoporosis and other osteolytic diseases.
