β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Bone research - 12(2024), 1 vom: 21. März, Seite 18 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Jie [VerfasserIn] |
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| Links: |
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| Themen: |
9Y8NXQ24VQ |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41413-024-00321-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370042174 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Anabolic Agents |2 NLM | |
| 650 | 7 | |a Propranolol |2 NLM | |
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| 700 | 1 | |a Zheng, Xuan-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Leng, Hui-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Dong-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Wan-Qiong |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Chun-Li |e verfasserin |4 aut | |
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