| 甲状旁腺激素经不同信号通路调节骨代谢的研究进展 |
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Received:October 20, 2020
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| 作者 | Author | 单位 | Unit | E-Mail |
| 宋蒙胜 |
SONG Meng-sheng |
中国科学院大学宁波华美医院骨科, 宁波 315010
宁波大学医学院, 宁波 315211 |
Department of Orthopaedics, Huamei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China |
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| 余霄 |
YU Xiao |
中国科学院大学宁波华美医院骨科, 宁波 315010 |
Department of Orthopaedics, Huamei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China |
yuxiao19@163.com |
| 戎鹏泽 |
RONG Peng-ze |
宁波大学医学院, 宁波 315211 |
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| 庞清江 |
PANG Qing-jiang |
中国科学院大学宁波华美医院骨科, 宁波 315010 |
Department of Orthopaedics, Huamei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, Zhejiang, China |
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| 期刊信息：《中国骨伤》2021年34卷，第6期，第584-588页 |
| DOI：10.12200/j.issn.1003-0034.2021.06.020 |
| 基金项目:浙江省医药卫生科技计划（编号：2018ky156）；宁波市自然科学基金（编号：2019A610242）；浙江省中医药科技计划（编号：2020ZB225）；中国科学院大学宁波华美医院"华美重点研究基金"（编号：2019HMZDKY14） |
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| 甲状旁腺激素是目前广泛应用于临床中的抗骨质疏松骨形成促进剂。然而，由于其小剂量、间歇性促进骨形成以及大剂量、连续性促进骨吸收的双向调节作用，使得甲状旁腺激素在骨质疏松症的治疗中有待进一步优化。因此，立足于甲状旁腺激素调节骨代谢的分子机制，总结甲状旁腺激素主要经如下信号通路调节骨代谢：（1）Gs/cAMP/PKA信号通路，是甲状旁腺激素调节骨组织代谢引起骨形成或骨吸收效应的主要机制。（2）Gq/11/PLC/PKC信号通路，其主要功能为抑制成骨作用。（3）nonPLC/PKC信号通路，目前认为其发挥成骨效应，但具体内容尚不完全明确。（4）β-arrestin信号通路，能通过受体脱敏及内吞机制仅产生成骨作用而无破骨的激活。对甲状旁腺激素激活的上述4条主要信号通路的内容及作用进行文献综述，以期找寻更好的骨形成促进剂。其中，SOST及Dickkopf-1单克隆抗体是新颖的靶向药物，特异性激活nonPLC/PKC信号通路或β-arrestin信号通路的甲状旁腺激素相关肽值得进一步开发和应用。 |
| [关键词]:甲状旁腺激素 信号通路 骨质疏松 |
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| Progress of parathyroid hormone regulating bone metabolism via different signaling pathways |
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| Abstract:Parathyroid hormone is one kind of osteoanabolic agents widely used in clinic for osteoporosis. However,parathyroid hormone needs to be further optimized in the treatment of osteoporosis due to its two-way regulatory effect of bone formation with low-dose intermittent treatmentand bone resorption with high-dosecontinuous treatment. Hence,based on the molecular mechanism of parathyroid hormone regulating bone metabolism,we conclude that parathyroid hormone regulates bone metabolism mainly through the following signaling pathways:(1) Gs/cAMP/PKA signaling pathway,whichis the main mechanism of parathyroid hormone regulating bone metabolism to lead to bone formation or bone resorption. (2) Gq/11/PLC/PKC signaling pathway,whose main function is to inhibit osteogenesis. (3) nonPLC/PKC signaling pathway,which is considered to playosteogenic effect,but whose specific content is not completely clear. (4) β-arrestin signaling pathway,which can only induceosteogenesis without osteoclastic activation byreceptor desensitization and endocytosis. In this work,we will review the specific contents and functions of the four main signaling pathways activated by parathyroid hormoneto find more optimalosteoanabolic agents. Among them,SOST and Dickkopf-1 monoclonal antibodies are novel targeted drugs. Parathyroid hormone-related peptide that specifically activates the nonPLC/PKC signaling pathway or β-arrestin signaling pathway is worthy of further development and application. |
| KEYWORDS:Parathyroid hormone Signaling pathway Osteoporosis |
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| 引用本文，请按以下格式著录参考文献： |
| 中文格式: | 宋蒙胜,余霄,戎鹏泽,庞清江.甲状旁腺激素经不同信号通路调节骨代谢的研究进展[J].中国骨伤,2021,34(6):584~588 |
| 英文格式: | SONG Meng-sheng,YU Xiao,RONG Peng-ze,PANG Qing-jiang.Progress of parathyroid hormone regulating bone metabolism via different signaling pathways[J].zhongguo gu shang / China J Orthop Trauma ,2021,34(6):584~588 |
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