Transforming growth factor alpha controls the transition from hypertrophic cartilage to bone during endochondral bone growth
Transforming growth factor alpha controls the transition from hypertrophic cartilage to bone during endochondral bone growth
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DOI：
10.1016/j.bone.2012.04.012
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发表时间：
2012-07-01
期刊：
影响因子：
4.1
通讯作者：
Beier, Frank
中科院分区：
文献类型：
--
作者：
Usmani, Shirine E.;Pest, Michael A.;Beier, Frank
我们最近发现转化生长因子α（TGFα）是一种与骨关节炎关节疾病相关的新型生长因子。然而，TGFa 在正常软骨和骨生理学中的作用尚未明确。目的：本研究的目的是通过研究 Tgfa 敲除小鼠来确定 TGF α 在骨骼发育中的作用。方法：在从新生儿到十周龄的几个发育阶段，检查 Tgfa 敲除小鼠及其对照同窝小鼠的大体骨骼和软骨生长板。结果：敲除小鼠出现骨骼生长迟缓和生长板肥厚区扩大。这些表型是短暂的，并在十周龄时自发消失。 TGFA 敲除生长板的软骨/骨界面处的破骨细胞也较少。此外，与对照组相比，敲除小鼠的软骨生长板中的 RUNX2、RANKL 和 MMP13 mRNA 表达量较低。结论：Tgfa 敲除小鼠的骨发育延迟，特别是肥大软骨向真骨转化的延迟。生长板肥大区的持续存在似乎是由肥大软骨细胞中 MMP13 和 RANKL 表达的减少以及由此导致的破骨细胞募集的减少介导的。总体而言，TGFa似乎是软骨内骨化过程中调节软骨向骨转化的重要生长因子。 (C) 2012 Elsevier Inc. 保留所有权利。
We have recently identified transforming growth factor alpha (TGF alpha) as a novel growth factor involved in the joint disease osteoarthritis. The role of TGFa in normal cartilage and bone physiology however, has not been well defined. Purpose: The objective of this study was to determine the role of TGF alpha in bone development through investigation of the Tgfa knockout mouse.Methods: The gross skeletons as well as the cartilage growth plates of Tgfa knockout mice and their control littermates were examined during several developmental stages ranging from newborn to ten weeks old.Results: Knockout mice experienced skeletal growth retardation and expansion of the hypertrophic zone of the growth plate. These phenotypes were transient and spontaneously resolved by ten weeks of age. Tgfa knockout growth plates also had fewer osteoclasts along the cartilage/bone interface. Furthermore, knockout mice expressed less RUNX2, RANKL, and MMP13 mRNA in their cartilage growth plates than controls did.Conclusions: Tgfa knockout mice experience a delay in bone development, specifically the conversion of hypertrophic cartilage to true bone. The persistence of the hypertrophic zone of the growth plate appears to be mediated by a decrease in MMP13 and RANKL expression in hypertrophic chondrocytes and a resulting reduction in osteoclast recruitment. Overall, TGFa appears to be an important growth factor regulating the conversion of cartilage to bone during the process of endochondral ossification. (C) 2012 Elsevier Inc. All rights reserved.