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重组人骨形态发生蛋白-4(BMP-4)刺激大鼠颅骨缝扩张内的细胞分化和骨形成。

Recombinant human bone morphogenetic protein-4 (BMP-4)-stimulated cell differentiation and bone formation within the expanding calvarial suture in rats.

作者信息

Shen Qingran, Zhu Songsong, Hu Jing, Geng Ning, Zou Shujuan

机构信息

State Key Laboratory of Oral Diseases, Department of Orthodontics, Sichuan University, Chengdu, China.

出版信息

J Craniofac Surg. 2009 Sep;20(5):1561-5. doi: 10.1097/SCS.0b013e3181b09cc1.

DOI:10.1097/SCS.0b013e3181b09cc1
PMID:19816296
Abstract

Suture expansion osteogenesis, which induces active bone formation within the distracted area by mechanical stress, provides an alternative form of treatment of some bone deficiency problems in craniofacial field, such as craniosynostosis, palate cleft, or narrow maxilla. However, how to stimulate new bone formation within the distracted area remains a great challenge. In this study, the effect of recombinant human bone morphogenetic protein (rhBMP-4) on bone formation induced by mechanical stimuli was investigated. The expanded midsagittal sutures of the rat calvaria were maintained in an organ culture system in the absence (control group) or presence (experimental group) of rhBMP-4 (25 or 50 ng/mL). Proliferating cell nuclear antigen, alkaline phosphatase (ALP) activity, and messenger RNA levels of core-binding factor alpha 1 (Cbfa1) and ALP were detected to determine the cell proliferation and differentiation. Bone formation within the suture was evaluated by histologic and fluorescent examination. No difference in the number of proliferating cell nuclear antigen-positive cells was found between the control and the experimental groups, whereas ALPase activity and messenger RNA levels of Cbfa1 and ALP in the experimental group were higher than that in the control group. Bone formation was accelerated in the rhBMP-4-treated group when compared with the control group. In addition, the amounts of bone formation and cell differentiation in response to 25 ng/mL of rhBMP-4 were almost equal to those induced by 50 ng/mL of rhBMP-4. Our results suggest that application of exogenous rhBMP-4 could enhance new bone formation within the rapid expanded sutures by stimulating osteoblast differentiation.

摘要

缝线牵张成骨通过机械应力在牵张区域诱导活跃的骨形成,为颅面领域一些骨缺损问题提供了一种替代治疗方式,如颅缝早闭、腭裂或上颌骨狭窄。然而,如何在牵张区域刺激新骨形成仍然是一个巨大的挑战。在本研究中,研究了重组人骨形态发生蛋白(rhBMP-4)对机械刺激诱导的骨形成的影响。将大鼠颅骨的扩大矢状缝在无rhBMP-4(对照组)或有rhBMP-4(实验组,25或50 ng/mL)的器官培养系统中维持。检测增殖细胞核抗原、碱性磷酸酶(ALP)活性以及核心结合因子α1(Cbfa1)和ALP的信使RNA水平,以确定细胞增殖和分化情况。通过组织学和荧光检查评估缝线内的骨形成。对照组和实验组之间增殖细胞核抗原阳性细胞数量没有差异,而实验组中Cbfa1和ALP的碱性磷酸酶活性和信使RNA水平高于对照组。与对照组相比,rhBMP-4处理组的骨形成加速。此外,25 ng/mL rhBMP-4诱导的骨形成量和细胞分化量几乎与50 ng/mL rhBMP-4诱导的相等。我们的结果表明,应用外源性rhBMP-4可通过刺激成骨细胞分化增强快速扩大的缝线内的新骨形成。

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