β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture  

作　　者：Jie Huang Tong Wu Yi-Rong Jiang Xuan-Qi Zheng Huan Wang Hao Liu Hong Wang Hui-Jie Leng Dong-Wei Fan Wan-Qiong Yuan Chun-Li Song 

机构地区：[1]Department of Orthopedics,Peking University Third Hospital,100191 Beijing,China [2]Beijing Key Laboratory of Spinal Disease,100191 Beijing,China [3]Engineering Research Center of Bone and Joint Precision Medicine,100191 Beijing,China

出　　处：《Bone Research》2024年第2期302-313,共12页骨研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.82330078,81874010);the National Key Research and Development Program(Grant Nos.2020YFC2009004,2021YFC2501700).

摘　　要：The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone formation.We found that fractures lead to increased sympathetic tone,enhanced osteoclast resorption,decreased osteoblast formation,and thus hastened systemic bone loss in ovariectomized(OVX)mice.However,the combined administration of parathyroid hormone(PTH)and theβ-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice.The effect of this treatment is superior to that of treatment with PTH or propranolol alone.In vitro,the sympathetic neurotransmitter norepinephrine(NE)suppressed PTH-induced osteoblast differentiation and mineralization,which was rescued by propranolol.Moreover,NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation,whereas these effects were reversed by propranolol.Furthermore,PTH increased the expression of the circadian clock gene Bmal1,which was inhibited by NE-βAR signaling.Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTHstimulated osteoblast differentiation.Taken together,these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

关 键 词：BLOCKER METABOLISM inhibited 

分 类 号：R683[医药卫生—骨科学]