| 胰岛素样生长因子1(IGF-1)通过抑制RUNX2促进骨折愈合的机制研究 |
| 投稿时间：2018-02-25 修订日期：2018-03-11 点此下载全文 |
| 引用本文：易知非,周芳,谢增如.胰岛素样生长因子1(IGF-1)通过抑制RUNX2促进骨折愈合的机制研究[J].医学研究杂志,2018,47(10):27-31 |
| DOI：
10.11969/j.issn.1673-548X.2018.10.009 |
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| 基金项目:国家自然科学基金资助项目（81660368） |
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| 中文摘要:目的 探讨IGF-1信号促进骨折愈合的分子机制。方法 建立IGF-1成骨细胞特异性敲除小鼠的骨折模型，三点弯曲试验分析IGF-1敲除组（KO）与对照组（Con）的最大载荷。通过Q-PCR和TRAP染色方法检测KO组和Con组成骨细胞分化指标的表达破骨细胞的个数。分离并培养来自KO组和Con组小鼠的骨髓基质细胞（BMSC），经瞬时转染si-RUNX2，采用Q-PCR和Western blot法检测转染前后BMSC细胞中成骨细胞分化指标的表达情况。结果 骨折后10天和21天，KO组的最大载荷明显低于Con组。与Con组相比，KO组愈伤组织的OCN和ALP表达显著降低，而RUNX2则明显提高，且TRAP阳性破骨细胞数显著减少，表明敲除IGF-1破坏了小鼠的骨折愈合能力。通过瞬时转染si-RUNX2于BMSC细胞，发现干扰RUNX2表达能够有效挽救因IGF-1敲除而破坏的成骨细胞分化潜能。表明RUNX2参与IGF-1信号调节的骨折愈合过程。结论 IGF-1能够诱导成骨细胞分化和破骨细胞形成，其诱导成骨细胞分化的机制可能是通过抑制RUNX2的表达，这为骨折愈合的机制提供新的理论依据。 |
| 中文关键词:骨折愈合 IGF-1 RUNX2 成骨细胞 破骨细胞 |
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| Mechanism of Insulin-like Growth Factor 1 (IGF-1) Promoting Fracture Healing by Inhibiting RUNX2 |
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| Abstract:Objective To investigate the molecular mechanism of IGF-1 promoting fracture healing. Methods The fracture model of osteoblast-specific IGF-1 knockout mice was established, and the maximum load of IGF-1 knockout group (KO) and control group (Con) were analyzed by three-point bending test. The makers of osteoblasts differentiation andnumber of osteoclasts of KO and Con group was detected by Q-PCR and TRAP staining. Bone marrow stromal cells from KO and Con mice were isolated and cultured, and transiently transfected with si-RUNX2, the markers of osteoblast differentiation in BMSC cells was detected by Q-PCR and western blot. Results At 10 days and 21 days after fracture, the maximum load in KO group was significantly lower than that in Con group. Compared with Con group, the expression of OCN and ALP in KO group decreased significantly, whereas RUNX2 increased significantly, and the number of TRAP positive osteoclasts decreased significantly, which indicated that IGF-1 knockdown impaired the fracture healing ability of mice. Via transient transfection si-RUNX2 into BMSC cells, interfering with RUNX2 expression can effectively rescue the osteoblast differentiation potential impaired by IGF-1 knockout. RUNX2 is implicated in the process of fracture healing with IGF-1 signaling. Conclusion IGF-1 can induce osteoblast differentiation and osteoclast formation. The possiblemechanism of IGF-1 inducing osteoblast differentiation is through inhibition of RUNX2 expression, which provides a new theoretical basis for the mechanism of fracture healing. |
| keywords:Fracture healing IGF-1 RUNX2 Osteoblasts Osteoclasts |
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