1. Academic Validation
  2. β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

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

  • Bone Res. 2024 Mar 21;12(1):18. doi: 10.1038/s41413-024-00321-z.
Jie Huang # 1 Tong Wu # 1 Yi-Rong Jiang 1 Xuan-Qi Zheng 1 Huan Wang 1 Hao Liu 1 Hong Wang 1 2 3 Hui-Jie Leng 1 2 3 Dong-Wei Fan 1 2 3 Wan-Qiong Yuan 1 2 3 Chun-Li Song 4 5 6
Affiliations

Affiliations

  • 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.
  • 4 Department of Orthopedics, Peking University Third Hospital, 100191, Beijing, China. schl@bjmu.edu.cn.
  • 5 Beijing Key Laboratory of Spinal Disease, 100191, Beijing, China. schl@bjmu.edu.cn.
  • 6 Engineering Research Center of Bone and Joint Precision Medicine, 100191, Beijing, China. schl@bjmu.edu.cn.
  • # Contributed equally.
Abstract

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 the β-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 PTH-stimulated 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.

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