骨质疏松研究热点:骨髓间充质干细胞分化命运
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第二军医大学附属长海医院创伤骨科,第二军医大学附属长海医院创伤骨科

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国家自然科学基金国际合作项目(8141101156),上海市科委生物医药专项(15411950600).


New focus on osteoporosis: differentiation fate of bone marrow-derived mesenchymal stem cells
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Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University,Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University

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    摘要:

    骨质疏松症是一种常见的代谢性骨病,以骨量减少、骨密度降低和骨微结构破坏为特征,容易发生脆性骨折,其发病率逐年增高。骨质疏松症发病与骨平衡的破坏有关,一方面破骨细胞活性增强、骨吸收加快,另一方面成骨细胞功能衰减、骨形成不足,最终导致净骨量丢失。成骨不足与骨髓间充质干细胞分化方向密切相关。在骨质疏松症患者中,骨髓间充质干细胞向脂肪方向分化增多,向成骨方向分化减少,其分化命运受BMP/Smad、Wnt、Notch、Hedgehog等多条信号通路调控,并涉及转录调控、转录后调控和表观遗传等多种调控机制,是目前研究的热点与焦点。未来研究可集中于寻找决定骨髓间充质干细胞分化方向的关键因子和间充质干细胞移植,为骨质疏松症的治疗提供新思路。

    Abstract:

    Osteoporosis is a frequently seen metabolic bone disease characterized by reduced bone mass, reduced bone mineral density and bone micro-structure destruction. Patients with osteoporosis are prone to brittle fractures, and the incidence of osteoporosis is increased annually. The pathogenesis of osteoporosis is related to the imbalance between osteoblasts and osteoclasts. On one hand, the activity of osteoclasts is increased, with high bone resorption; on the other hand, the function of osteoblasts is attenuated, with low osteogenesis; and finally the two reasons lead to loss of net bone mass. Osteogenesis is closely related to the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). In osteoporotic patients, the adipogenic differentiation of BMSCs is increased and the osteogenic differentiation is decreased. The differentiation fate of BMSCs is regulated by BMP/Smad, Wnt, Notch, Hedgehogs and other signal pathways, involving microRNAs, transcription factors, epigenetic and other regulatory mechanisms, which is a focus in current research. The future studies need to focus on finding the key factors in determining the differentiation fate of BMSCs and BMSCs transplantation, so as to cast new lights on the treatment of osteoporosis.

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  • 收稿日期:2016-12-12
  • 最后修改日期:2017-04-09
  • 录用日期:2017-04-17
  • 在线发布日期: 2017-05-02
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