TGF-β, BMPS, and their signal transducing mediators, Smads, in rat fracture healing

TGF-β, BMPS, and their signal transducing mediators, Smads, in rat fracture healing
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TGF-β、BMPS 及其信号转导介质 Smads 在大鼠骨折愈合中的作用

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发表时间:
2002
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通讯作者:
W. Walsh
W. Walsh
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作者:
Yan Yu;Jia;P. Chapman;W. Walsh

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SMADs是转化生长因子-β(转化生长因子-β)和骨形态发生蛋白(BMP)的胞浆信号转导分子。它们与骨折愈合的关系尚不清楚。本研究采用免疫组织化学方法检测了Smads、转化生长因子-β和骨形态发生蛋白在啮齿动物骨折模型中的表达。在骨折部位增厚的骨膜和骨髓中的成骨细胞在第3天检测到转化生长因子-β、骨形态发生蛋白-2、4和7、共同介体SMAD(SMAD4)和受体调节的SMAD1、2、3和5过度表达,而抑制性SMAD(SMAD6)水平较低。在第10天,骨折骨痂中Smad6显著增加,Smad2、Smad3和Smad4持续升高,而Smad1和Smad5下降。Smad7仅在血管内皮细胞表达。到第28天,当新骨取代骨折骨痂时,所有的蛋白质调节因子都减少了,接近对照水平。在骨折愈合过程中,Smads1和5的表达模式与BMPs-2和7相似,而Smads2和3的表达与转化生长因子-β的表达平行。Smad家族与BMPs和转化生长因子-β相关,可能在大鼠骨折愈合的早期发挥重要作用。《生物医学杂志》2002年版60:392-397;DOI 10.1002/jbm.1289
Smads are cytoplasmic signal transducers of transforming growth factor-β (TGF-β) and bone morphogenetic proteins (BMPs). Their relation to fracture healing is unknown. This study examined the temporal protein expression of Smads, together with TGF-β and BMPs, using immunohistochemistry in a rodent fracture model. Over-expression of TGF-β, BMPs-2, 4, and 7, common-mediator Smad (Smad4), and receptor-regulated Smads (Smads1, 2, 3, and 5) versus lower levels of inhibitory Smad (Smad6), were detected at day 3 in osteogenic cells in the thickened periosteum and bone marrow at the fracture sites. At day 10, Smad6 increased dramatically, Smad2, Smad3, and Smad4 remained elevated while Smad1 and Smad5 decreased in the fracture callus. Smad7 was expressed only in vascular endothelial cells. By day 28, when new bone had replaced the fracture callus, all the protein regulators decreased, approaching control levels. During fracture healing, the expression patterns of Smads1 and 5 were similar to that of BMPs-2 and 7 whereas the expression of Smads2 and 3 was parallel with that of TGF-β. The Smad family, associated with BMPs and TGF-β, may play an important role in the early stage of rat fracture healing. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 392–397, 2002; DOI 10.1002/jbm.1289