Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trablecular bone
Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trablecular bone
复制标题
DOI：
10.1073/pnas.0608449104
复制
发表时间：
2007-04-10
影响因子：
11.1
通讯作者：
Lanske, Beate
中科院分区：
文献类型：
--
作者：
Maeda, Yukiko;Nakamura, Eiichiro;Lanske, Beate
印度刺猬 (Ihh) 对于产前软骨内骨形成过程中的软骨细胞和成骨细胞增殖/分化至关重要。然而，各种 thh 消融突变小鼠的早期致死性阻碍了对其在出生后骨骼生长和发育中的作用的进一步分析。在这项研究中，我们描述了小鼠模型的生成和表征，其中 lhh 基因以时间/空间特异性方式成功地从出生后软骨细胞中消除；出生后 Ihh 缺失导致柱状结构丧失、血管过早侵袭以及生长板中异位肥大软骨细胞的形成。此外，长骨关节面的破坏和各种软骨骨生长板的过早融合是明显的，导致突变小鼠出现侏儒症。更重要的是，这些突变小鼠随着时间的推移表现出骨小梁的持续丢失，同时伴随着成骨细胞中 Wnt 信号传导的减少。这些结果首次证明，出生后软骨细胞来源的 Ihh 对于维持生长板和关节面至关重要，并且是维持小梁骨和骨骼生长所必需的。
Indian hedgehog (Ihh) is essential for chondrocyte and osteolblast proliferation/differentiation during prenatal enclochondral bone formation. The early lethality of various thh-ablated mutant mice, however, prevented further analysis of its role in postnatal bone growth and development. In this study, we describe the generation and characterization of a mouse model in which the lhh gene was successfully ablated from postnatal chondrocytes in a temporal/ spatial-specific manner; postnatal deletion of Ihh resulted in loss of columnar structure, premature vascular invasion, and formation of ectopic hypertrophic chondrocytes in the growth plate. Furthermore, destruction of the articular surface in long bones and premature fusion of growth plates of various enclochondral bones was evident, resulting in dwarfism in mutant mice. More importantly, these mutant mice exhibited continuous loss of trabecular bone over time, which was accompanied by reduced Wnt signaling in the osteoblastic cells. These results demonstrate, for the first time, that postnatal chond rocyte-derived Ihh is essential for maintaining the growth plate and articular surface and is required for sustaining trabecular bone and skeletal growth.