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肌腱干细胞的机械生物学反应:肌腱稳态的意义和肌腱病发病机制。

Mechanobiological response of tendon stem cells: implications of tendon homeostasis and pathogenesis of tendinopathy.

机构信息

MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, 210 Lothrop Street, BST, E1640, Pittsburgh, Pennsylvania 15213, USA.

出版信息

J Orthop Res. 2010 May;28(5):639-43. doi: 10.1002/jor.21046.

DOI:10.1002/jor.21046
PMID:19918904
Abstract

Tendons are constantly subjected to mechanical loading in vivo. Recently, stem cells were identified in human, mouse, and rabbit tendons, but the mechanobiological responses of tendon stem cells (TSCs) are still undefined. Using an in vitro system capable of mimicking in vivo loading conditions, it was determined that mechanical stretching increased TSC proliferation in a stretching magnitude-dependent manner. Moreover, low mechanical stretching at 4% ("clamp-to-clamp" engineering strain) promoted differentiation of TSCs into tenocytes, whereas large stretching at 8% induced differentiation of some TSCs into adipogenic, chondrogenic, and osteogenic lineages, as indicated by upregulated expression of marker genes for adipocytes, chondrocytes, and osteocytes. Thus, low mechanical stretching may be beneficial to tendons by enabling differentiation of TSCs into tenocytes to maintain tendon homeostasis. However, large mechanical loading may be detrimental, as it directs differentiation of TSCs into non-tenocytes in tendons, thus resulting in lipid accumulation, mucoid formation, and tissue calcification, which are typical features of tendinopathy at later stages.

摘要

肌腱在体内不断受到机械负荷。最近,在人类、小鼠和兔肌腱中发现了干细胞,但肌腱干细胞(TSC)的力学生物学反应仍未确定。使用一种能够模拟体内加载条件的体外系统,确定机械拉伸以拉伸幅度依赖的方式增加 TSC 的增殖。此外,4%的低机械拉伸(“夹到夹”工程应变)促进 TSCs 分化为腱细胞,而 8%的大拉伸诱导一些 TSCs 分化为成脂细胞、成软骨细胞和成骨细胞谱系,这表明成脂细胞、成软骨细胞和成骨细胞的标记基因表达上调。因此,低机械拉伸可能通过使 TSCs 分化为腱细胞来维持肌腱的内稳态而有益于肌腱。然而,大的机械加载可能是有害的,因为它促使 TSCs 在肌腱中分化为非腱细胞,从而导致脂质积累、黏液形成和组织钙化,这是肌腱病后期的典型特征。

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