TGF-β Stimulates Endochondral Differentiation after Denervation.

TGF-β Stimulates Endochondral Differentiation after Denervation.
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DOI:
10.7150/ijms.17364
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发表时间:
2017
影响因子:
3.6
通讯作者:
Du H
Du H
中科院分区:
医学4区
文献类型:
--
作者:
Li Y;Tian AY;Ophene J;Tian MY;Yao Z;Chen S;Li H;Sun X;Du H

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转化生长因子β(Transforming growth factor beta,TGF-β)是一种多功能蛋白,可诱导软骨特异性分子的基因表达,但其在软骨形成过程中的确切作用尚不清楚。由于最近的研究表明,TGF-β可以促进软骨前体细胞分化成软骨细胞,我们试图确定TGF-β是否可以防止实验模型中去神经诱导的软骨内骨形成减少。小鼠每天用重组人TGF-β1(rhTGF-β1)处理3周。我们发现,rhTGF-β1不仅阻止失神经诱导的II型胶原、X型胶原、聚集蛋白聚糖、印度刺猬蛋白和甲状旁腺相关肽基因表达的减少,而且还协同软骨内分化。这些结果表明,TGF-β的短期全身施用通过刺激软骨内分化基本上防止了去神经诱导的软骨内骨形成的减少。在动物模型中,TGF-β对去神经后内软骨骨形成的分子生物学机制将在进一步的研究中寻求潜在的治疗应用。
Transforming growth factor beta (TGF-β) is a multifunctional protein that induces gene expression of cartilage-specific molecules, but its exact role in the process of chondrogenesis is unclear. Because recent studies suggest that TGF-β can facilitate chondrogenic precursor cells differentiating into chondrocytes, we sought to determine whether TGF-β prevents denervation-induced reduction of endochondral bone formation in an experimental model. Mice were treated daily with recombinant human TGF-β1 (rhTGF-β1) for 3 weeks. We found that rhTGF-β1 not only prevented denervation-induced reduction of gene expression of type II collagen, type X collagen, aggrecan, Indian hedgehog, and parathyroid hormone-related peptide, but also synergized endochondral differentiation. These results demonstrate that short-term systemic administration of TGF-β substantially prevents denervation-induced reduction of endochondral bone formation via stimulating endochondral differentiation. Potential therapeutic applications will be pursued in further studies that address the molecular biological mechanism of TGF-β on endochodral bone formation after denervation in animal models.