Wnt-mediated reciprocal regulation between cartilage and bone development during endochondral ossification
Wnt-mediated reciprocal regulation between cartilage and bone development during endochondral ossification
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软骨内骨化过程中Wnt介导的软骨与骨发育之间的相互调节
DOI：
10.1016/j.bone.2012.12.016
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发表时间：
2013-04-01
期刊：
影响因子：
4.1
通讯作者：
Guo, Xizhi
中科院分区：
文献类型：
--
作者：
Lu, Cheng;Wan, Yong;Guo, Xizhi
Wnt信号传导在骨骼发育和出生后骨重建中的作用被广泛研究，主要基于β-连环蛋白操纵的遗传方法。然而，考虑到它们的独立功能，对β-连环蛋白的要求与对Wnt的要求不同。在这里，我们通过分别产生软骨或骨特异性Wls缺失小鼠来研究Wnt蛋白在两种组织中的作用。通过Col 2-Cre消耗WL 5，这将阻断软骨细胞和软骨膜中的Wnt分泌，延迟生长板中的软骨细胞肥大并损害软骨膜成骨。软骨细胞中Ms的丢失也扰乱了增殖的软骨细胞形态和分裂方向，这与在Wnt 5a敲除小鼠中观察到的缺陷相似。另一方面，Col 1-Cre灭活成骨细胞中的Wls导致生长板软骨-骨连接处的肥大区变短，TRAP阳性细胞数量增加，同时骨量减少。总之，我们的研究表明，Wnt蛋白不仅调节软骨细胞群体内的分化和细胞通讯，而且还介导生长板中软骨细胞和成骨细胞之间的交叉调节。(C)2012 Elsevier Inc. All rights reserved.
The role of Wnt signaling is extensively studied in skeletal development and postnatal bone remodeling, mostly based on the genetic approaches of beta-catenin manipulation. However, given their independent function, a requirement for beta-catenin is not the same as that for Wnt. Here, we investigated the effect of Wnt proteins in both tissues through generating cartilage- or bone-specific Wls null mice, respectively. Depletion of WL5 by Col2-Cre, which would block Wnt secretion in the chondrocytes and perichondrium, delayed chondrocyte hypertrophy in the growth plate and impaired perichondrial osteogenesis. Loss of Ms in chondrocytes also disturbed the proliferating chondrocyte morphology and division orientation, which was similar to the defect observed in Wnt5a null mice. On the other hand, inactivation of Wls in osteoblasts by Col1-Cre resulted in a shorter hypertrophic zone and an increase of TRAP positive cell number in the chondro-osseous junction of growth plate, coupled with a decrease in bone mass. Taken together, our studies reveal that Wnt proteins not only modulate differentiation and cellular communication within populations of chondrocytes, but also mediate the cross regulation between the chondrocytes and osteoblasts in growth plate. (C) 2012 Elsevier Inc. All rights reserved.