赵锐 王译晗 朱悦 陶琳 单军

【摘要】 骨质疏松症是临床常见的代谢性骨病。骨质疏松的发生是由各种原因导致的成骨细胞介导的骨生成减少或破骨细胞介导的骨吸收增加。骨生成作用主要由成熟的成骨细胞完成，成骨细胞主要来源于间充质干细胞（mesenchymal stem cells，MSCs），在一系列信号通路及细胞因子等的调控下，MSCs可以分化为成骨细胞，进而发挥骨生成作用。因此增强成骨细胞的分化能力至关重要。目前已知多条信号通路参与到MSCs向成骨细胞分化的过程中，例如Wnt/β-catenin、BMP-Smads、Hedgehog、Notch、PI3K/AKT、MAPKs信号通路等，同时Runx2、Osterix或PPARγ等关键转录因子也在成骨分化过程中起到重要调控作用，这些信号通路与转录因子的激活或抑制影响着MSCs向成骨细胞或脂肪细胞的分化倾向，但这些信号通路与转录因子之间是否存在相互联系，以及它们是如何协同发挥调控成骨细胞分化的作用目前尚不明确。因此，本文针对成骨细胞分化相关重要信号通路以及转录因子研究进展做一综述，为临床上大量的骨代谢异常相关疾病寻找发病机制以及治疗靶点。

【关键词】 成骨分化 信号通路 Runx2 Osterix

Advances in Signaling Pathways and Cytokines Regulating Osteoblastic Differentiation/ZHAO Rui， WANG Yihan， ZHU Yue， TAO Lin， SHAN Jun. //Medical Innovation of China， 2021， 18（05）： -176

[Abstract] Osteoporosis is a common clinical metabolic osteopathy. Osteoporosis occurs due to decreasing of bone formation by osteoblasts or increasing of bone resorption by osteoclasts. Bone formation is done by mature osteoblasts， which are mainly derived from mesenchymal stem cells （MSCs）. MSCs can differentiate into osteoblasts under the control of a series of signalling pathways and transcription factors. Therefore， it is important to enhance the differentiation of osteoblasts. Several signalling pathways are known to be involved in MSCs differentiation into osteoblasts， such as Wnt/β-catenin， BMP-Smads， Hedgehog， Notch， PI3K/AKT， MAPKs signalling pathways， meanwhile transcription factors such as Runx2， Osterix and PPARγ also play an important regulatory role in osteoblast differentiation. The activation or suppression of these signalling pathways and transcription factors affect tendency of MSCs differentiation into osteoblasts or fat cells， but it is not clear whether these signalling pathways and transcription factors are related to each other and how they work together to regulate osteoblast differentiation. Therefore， this paper makes a review of the important signalling pathways and transcription factors related to osteoblast differentiation， and seeks the pathogenesis and treatment targets for a large number of bone metabolic abnormality-related diseases in clinical.

[Key words] Osteoblast differentiation Signalling pathway Runx2 Osterix

First-authors address： Shenyang Orthopedic Hospital， Shenyang 110044， China

doi：10.3969/j.issn.1674-4985.2021.05.043

骨質疏松症是临床常见的代谢性骨病，一般表现为骨量减少、骨脆性增加，进而导致骨折风险增高等。成骨细胞介导的骨生成与破骨细胞介导的骨吸收之间的平衡维持着骨的稳态[1]。骨质疏松的发生由各种原因导致这种平衡被打破，出现成骨细胞介导的骨生成降低或者破骨细胞介导的骨吸收增加。骨生成作用主……