Altered fracture callus formation in chondromodulin-I deficient mice
Altered fracture callus formation in chondromodulin-I deficient mice
复制标题
DOI：
10.1016/j.bone.2008.08.111
复制
发表时间：
2008-12-01
期刊：
影响因子：
4.1
通讯作者：
Yasui, Natsuo
中科院分区：
文献类型：
--
作者：
Yukata, Kiminori;Matsui, Yoshito;Yasui, Natsuo
软骨调节素-I（Chondromodulin-I，Chm-I）是一种糖蛋白，在体外刺激软骨细胞生长，抑制血管生成。缺乏Chm 1基因的小鼠在成熟阶段的心脏瓣膜中显示异常的骨代谢和病理性血管生成，尽管它们在胚胎发生期间的软骨内骨形成或在生长期间的软骨发育中正常发育而没有畸变。这些发现表明，Chm-I在应力条件下是至关重要的，例如通过骨折骨痂的软骨内骨化进行骨修复。我们进行了本研究，以检查的表达和作用的Chm-I在骨修复中使用稳定的胫骨骨折模型，并比较骨折愈合的Chm 1基因敲除（Chm 1（-/-））小鼠与野生型小鼠。Chm-I mRNA和蛋白在骨折愈合的修复期定位于外软骨骨痂。放射学检查显示Chm 1（-/-）小鼠骨折愈合延迟，尽管骨折部位被内外老茧覆盖。通过X型胶原α 1（Col 10a 1）表达和软骨基质总量的显著减少来判断，Chm 1无效突变减少了外部软骨愈伤组织的形成。有趣的是，在Chm 1（-/-）小鼠中，骨膜骨痂中的大多数软骨细胞未能分化为成熟软骨细胞，而皮质之间的软骨细胞的肥大成熟不受影响。这些结果表明，Chm-I参与骨膜软骨细胞的肥大成熟。虽然Chm-I对骨骼的直接影响尚不清楚，但在Chm 1（-/-）小鼠中，骨痂形成增加，而外部软骨骨痂减少。我们的结论是，在没有Chm 1，主要的初级骨愈合发生由于减少软骨愈伤组织，而不是直接影响成骨功能，导致延迟愈合诱导的间接影响。(C)2008年爱思唯尔公司All rights reserved.
Chondromodulin-I (Chm-I) is a glycoprotein that stimulates the growth of chondrocytes and inhibits angiogenesis in vitro. Mice lacking the Chm1 gene show abnormal bone metabolism and pathological angiogenesis in cardiac valves in the mature stage although they develop normally without aberrations in endochondral bone formation during embryogenesis or in cartilage development during growth. These findings indicate that Chm-I is critical under conditions of stress such as bone repair through endochondral ossification of a fracture callus. We carried out the present study to examine the expression and role of Chm-I in bone repair using a stabilized tibial fracture model, and compared fracture healing in Chm1 knockout (Chm1(-/-)) mice with that in wild-type mice. Chm-I mRNA and protein localized in the external cartilaginous callus in the reparative phase of fracture healing. Radiological examination showed a delayed union in Chm1(-/-) mice although the fracture site was covered with both external and internal calluses. Chm1 null mutation reduced external cartilaginous callus formation as judged by marked decrease of type X collagen alpha 1 (Col10a1) expression and the total amount of cartilage matrix. Interestingly, the majority of chondrocytes in the periosteal callus failed to differentiate into Mature chondrocytes in Chm1(-/-) mice, while the hypertrophic maturation of chondrocytes between the cortices was not affected. These results suggest that Chm-I is involved in hypertrophic maturation of periosteal chondrocytes. Although a direct effect of Chm-I on bones is still unclear, bonycallus formation was increased while external cartilaginous callus decreased in Chm1(-/-) mice. We conclude that in the absence of Chm1, predominant primary bone healing occurs due to an indirect effect induced by reduction of cartilaginous callus rather than to a direct effect on osteogenic function, resulting in a delayed union. (C) 2008 Elsevier Inc. All rights reserved.