中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (13): 3350-3358.doi: 10.12307/2026.307

• 干细胞综述 stem cell review • 上一篇    下一篇

骨髓间充质干细胞成骨-成脂分化失衡与股骨头坏死:从分子机制到治疗策略

张世磊1,2,秦川洪1,2,王建旭1,2,孙  水1,2   

  1. 1山东第一医科大学附属省立医院骨关节科,山东省济南市   250021;2医学科技创新中心骨科实验室,山东第一医科大学(山东省医学科学院),山东省济南市   250117
  • 接受日期:2025-08-09 出版日期:2026-05-08 发布日期:2025-12-26
  • 通讯作者: 孙水,博士,教授,山东第一医科大学附属省立医院骨关节科,山东省济南市 250021;医学科技创新中心骨科实验室,山东第一医科大学(山东省医学科学院),山东省济南市 250117
  • 作者简介:张世磊,男,1999年生,山东省泰安市人,汉族,2025年山东第一医科大学毕业,硕士,主要从事骨科学方向研究。

Osteogenic-adipogenic differentiation imbalance of bone marrow mesenchymal stem cells and osteonecrosis of the femoral head: from molecular mechanisms to therapeutic strategies

Zhang Shilei1, 2, Qin Chuanhong1, 2, Wang Jianxu1, 2, Sun Shui1, 2   

  1. 1Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China; 2Orthopedic Research Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan 250117, Shandong Province, China
  • Accepted:2025-08-09 Online:2026-05-08 Published:2025-12-26
  • Contact: Sun Shui, MD, PhD, Professor, Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China; Orthopedic Research Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan 250117, Shandong Province, China
  • About author:Zhang Shilei, MS, Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China; Orthopedic Research Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan 250117, Shandong Province, China

摘要:

文题释义:

骨髓微环境:是由骨髓间充质干细胞、内皮细胞、交感神经系统神经纤维、辅助免疫细胞(如T淋巴细胞和单核细胞)及其分泌的细胞因子共同构成的动态网络系统,通过细胞间相互作用与分子调控机制,维持骨髓稳态并协调造血、骨代谢及免疫调节等关键生理功能。
干细胞疗法:是一种通过直接移植干细胞或干细胞与生物材料支架相结合等方式,以修复受损组织、替代功能缺失细胞、调节免疫反应或改善病理微环境的生物医学策略。

摘要
背景:股骨头坏死是一种常见的骨科疾病,其致残率高,临床特征为股骨头塌陷,导致严重髋关节疼痛和功能丧失。骨髓间充质干细胞具有多向分化潜能,其分化方向包括成骨细胞、脂肪细胞、软骨细胞等。在酒精、皮质激素等病理刺激下,成骨和成脂分化之间的动态均衡被破坏,可引起脂肪细胞的异常积累和骨形成的减少,最终导致股骨头坏死。
目的:重点解析股骨头坏死的分子机制,特别关注骨髓间充质干细胞的核心作用,并深入探讨脂肪细胞对疾病发展进程的影响。
方法:检索PubMed数据库,检索词“osteonecrosis of the femoral head,bone marrow mesenchymal stem cells,osteogenic differentiation,adipogenic differentiation,bone marrow adipose tissue,adipokines”,检索时限从建库至2025年6月。根据纳入与排除标准,最终纳入81文献进行综述。

结果与结论:汇总研究后发现,Wnt、转化生长因子β/骨形态发生蛋白超家族、磷脂酰肌醇3激酶/蛋白激酶B等信号通路,联合多种RNA分子,共同调控骨髓间充质干细胞的成骨/脂分化平衡。各信号通路通过靶向关键转录因子,如成骨相关的Runt相关转录因子2,成脂相关的过氧化物酶体增殖物激活受体γ及CCAAT增强子结合蛋白,从而实现对细胞行为的精确调控。此外,脂肪细胞及其分泌的细胞因子,如瘦素和脂联素等,亦可通过旁分泌作用影响股骨头坏死的发展进程。文章通过聚焦骨髓间充质干细胞和脂肪细胞的相互作用阐述了股骨头坏死的发病机制,并在当前研究进展的基础上展望了未来干预方向和治疗策略。

https://orcid.org/0009-0004-9310-6134 (张世磊) 
中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 股骨头坏死, 骨髓间充质干细胞, 信号通路, 脂肪因子, 脂肪细胞, 骨髓微环境, 分化平衡, 干细胞疗法

Abstract: BACKGROUND: Osteonecrosis of the femoral head is a common orthopedic condition that can lead to significant disability. A key feature of this disease is the collapse of the femoral head, causing severe hip pain and loss of function. Bone marrow mesenchymal stem cells can differentiate into multiple cell types, including osteoblasts, adipocytes, and chondrocytes. Pathological factors like alcohol and corticosteroids disrupt the balance between osteogenic and adipogenic differentiation. This leads to excessive fat accumulation and reduced bone formation, ultimately contributing to osteonecrosis of the femoral head. 
OBJECTIVE: To focus on elucidating molecular mechanisms underlying osteonecrosis of the femoral head with a particular focus on the role of bone marrow mesenchymal stem cells, and further discuss the implications of adipocytes.
METHODS: PubMed was searched for articles published from database inception to June 2025, using “osteonecrosis of the femoral head, bone marrow mesenchymal stem cells, osteogenic differentiation, adipogenic differentiation, bone marrow adipose tissue, adipokines.” Following the inclusion and exclusion criteria, 81 relevant articles were selected for comprehensive analysis.
RESULTS AND CONCLUSION: A review of research shows that Wnt, transforming growth factor-β/bone morphogenetic protein superfamily, and phosphatidylinositol 3-kinase/protein kinase B signaling pathways, along with various RNA molecules, play a role in regulating the balance between osteogenic and adipogenic differentiation in bone marrow mesenchymal stem cells. These pathways precisely control cell behavior by targeting key transcription factors, such as Runt-related transcription factor 2 for bone formation and peroxisome proliferator-activated receptor γ and CCAAT enhancer binding protein for fat cell development. Furthermore, adipocytes and the signaling molecules they release, such as leptin and adiponectin, can also affect the progression of osteonecrosis of the femoral head through paracrine signaling. This article explains how interactions between bone marrow mesenchymal stem cells and adipocytes contribute to the development of osteonecrosis of the femoral head and, based on current research, suggests potential future interventions and treatment strategies.

Key words: ">osteonecrosis of the femoral head, bone marrow mesenchymal stem cell, signaling pathway, adipokine, adipocyte, bone marrow microenvironment, differentiation balance, stem cell therapy

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