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

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING Bone Research Pub Date : 2024-03-21 DOI:10.1038/s41413-024-00321-z
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
{"title":"β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture","authors":"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","doi":"10.1038/s41413-024-00321-z","DOIUrl":null,"url":null,"abstract":"<p>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 <i>Rankl</i> 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 <i>Bmal1</i>, which was inhibited by NE-βAR signaling. <i>Bmal1</i> 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.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"24 1","pages":""},"PeriodicalIF":14.3000,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bone Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41413-024-00321-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

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.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
β-受体阻滞剂可增强骨质疏松性骨折后 PTH 的合成代谢作用
自律神经系统在调节骨代谢方面起着至关重要的作用,交感神经的激活会刺激骨吸收并抑制骨形成。我们发现,骨折会导致交感神经张力增加、破骨细胞吸收增强、成骨细胞形成减少,从而加速卵巢切除(OVX)小鼠的全身骨质流失。然而,联合使用甲状旁腺激素(PTH)和β受体阻滞剂普萘洛尔能显著促进卵巢切除小鼠全身骨形成和骨质疏松性骨折愈合。这种治疗效果优于单独使用 PTH 或普萘洛尔的治疗。在体外,交感神经递质去甲肾上腺素(NE)抑制了 PTH 诱导的成骨细胞分化和矿化,而普萘洛尔可挽救这种抑制作用。此外,去甲肾上腺素降低了 PTH 诱导的 Runx2 的表达,但增强了 Rankl 的表达以及 PTH 刺激的成骨细胞对破骨细胞分化的影响,而普萘洛尔可逆转这些影响。此外,PTH 增加了昼夜节律钟基因 Bmal1 的表达,而 NE-βAR 信号传导抑制了 Bmal1 的表达。Bmal1 基因敲除阻断了普萘洛尔对 NE 诱导的 PTH 刺激成骨细胞分化下降的挽救作用。综上所述,这些结果表明,普萘洛尔通过阻断交感神经信号对PTH合成代谢的负面影响,增强了PTH在预防骨质疏松性骨折后全身骨丢失方面的合成代谢作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
期刊最新文献
KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated m6A modification of ATG4a to promote NPCs senescence and IVDD progression Engineering bone/cartilage organoids: strategy, progress, and application Bone loss with aging is independent of gut microbiome in mice Inhibition of sympathetic tone via hypothalamic descending pathway propagates glucocorticoid-induced endothelial impairment and osteonecrosis of the femoral head IRF1-mediated upregulation of PARP12 promotes cartilage degradation by inhibiting PINK1/Parkin dependent mitophagy through ISG15 attenuating ubiquitylation and SUMOylation of MFN1/2.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1