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骨细胞特异性分子机制在机械转导调节中的作用——一项系统综述

The role of osteocytes-specific molecular mechanism in regulation of mechanotransduction - A systematic review.

作者信息

Li Meng Chen Michelle, Chow Simon Kwoon Ho, Wong Ronald Man Yeung, Qin Ling, Cheung Wing Hoi

机构信息

Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China.

The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China.

出版信息

J Orthop Translat. 2021 May 13;29:1-9. doi: 10.1016/j.jot.2021.04.005. eCollection 2021 Jul.

Abstract

BACKGROUND

Osteocytes, composing over 90% of bone cells, are well known for their mechanosensing abilities. Aged osteocytes with impaired morphology and function are less efficient in mechanotransduction which will disrupt bone turnover leading to osteoporosis. The aim of this systematic review is to delineate the mechanotransduction mechanism at different stages in order to explore potential target for therapeutic drugs.

METHODS

A systematic literature search was performed in PubMed and Web of Science. Original animal, cell and clinical studies with available English full-text were included. Information was extracted from the included studies for review.

RESULTS

The 26 studies included in this review provided evidence that mechanical loading are sensed by osteocytes via various sensing proteins and transduced to different signaling molecules which later initiate various biochemical responses. Studies have shown that osteocyte plasma membrane and cytoskeletons are emerging key players in initiating mechanotransduction. Bone regulating genes expressions are altered in response to load sensed by osteocytes, but the genes involved different signaling pathways and the spatiotemporal expression pattern had made mechanotransduction mechanism complicated. Most of the included studies described the important role of osteocytes in pathways that regulate mechanosensing and bone remodeling.

CONCLUSIONS

This systematic review provides an up-to-date insight to different steps of mechanotransduction. A better understanding of the mechanotransduction mechanism is beneficial in search of new potential treatment for osteoporotic patients. By delineating the unique morphology of osteocytes and their interconnected signaling network new targets can be discovered for drug development.

TRANSLATIONAL POTENTIAL OF THIS ARTICLE

This systematic review provides an up-to-date sequential overview and highlights the different osteocyte-related pathways and signaling molecules during mechanotransduction. This allows a better understanding of mechanotransduction for future development of new therapeutic interventions to treat patients with impaired mechanosensitivity.

摘要

背景

骨细胞占骨细胞总数的90%以上,以其机械传感能力而闻名。形态和功能受损的衰老骨细胞在机械转导方面效率较低,这将破坏骨转换,导致骨质疏松症。本系统综述的目的是描述不同阶段的机械转导机制,以探索治疗药物的潜在靶点。

方法

在PubMed和Web of Science上进行了系统的文献检索。纳入了具有可用英文全文的原始动物、细胞和临床研究。从纳入的研究中提取信息进行综述。

结果

本综述纳入的26项研究提供了证据,表明机械负荷由骨细胞通过各种传感蛋白感知,并转导至不同的信号分子,随后引发各种生化反应。研究表明,骨细胞质膜和细胞骨架在启动机械转导中发挥着关键作用。骨调节基因的表达会因骨细胞感知的负荷而改变,但涉及不同信号通路的基因及其时空表达模式使机械转导机制变得复杂。大多数纳入的研究描述了骨细胞在调节机械传感和骨重塑途径中的重要作用。

结论

本系统综述提供了对机械转导不同步骤的最新见解。更好地理解机械转导机制有助于寻找骨质疏松症患者的新潜在治疗方法。通过描绘骨细胞的独特形态及其相互连接的信号网络,可以发现药物开发的新靶点。

本文的转化潜力

本系统综述提供了最新的顺序概述,并突出了机械转导过程中不同的骨细胞相关途径和信号分子。这有助于更好地理解机械转导,为未来开发治疗机械敏感性受损患者的新治疗干预措施提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef1/8138679/32eacecbc5c3/gr1.jpg

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