Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
Bone. 2013 Apr;53(2):566-74. doi: 10.1016/j.bone.2012.12.016. Epub 2012 Dec 27.
The role of Wnt signaling is extensively studied in skeletal development and postnatal bone remodeling, mostly based on the genetic approaches of β-catenin manipulation. However, given their independent function, a requirement for β-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 Wls 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 Wls 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.
Wnt 信号通路在骨骼发育和出生后骨重塑中起着广泛的作用，其研究主要基于β-连环蛋白调控的遗传方法。然而，鉴于它们的独立功能，β-连环蛋白的需求与 Wnt 不同。在这里，我们通过分别生成软骨特异性或骨特异性 Wls 敲除小鼠，研究了 Wnt 蛋白在这两种组织中的作用。Col2-Cre 介导的 Wls 耗竭会阻断软骨细胞和成软骨细胞中的 Wnt 分泌，从而延迟生长板中的软骨细胞肥大，并损害成软骨细胞成骨。软骨细胞中 Wls 的缺失也扰乱了增殖性软骨细胞的形态和分裂方向，这与 Wnt5a 缺失小鼠观察到的缺陷相似。另一方面，Col1-Cre 介导的成骨细胞中 Wls 的失活导致生长板软骨-骨交界处的肥大区变短，TRAP 阳性细胞数量增加，同时骨量减少。总之，我们的研究揭示了 Wnt 蛋白不仅调节软骨细胞群体中的分化和细胞通讯，还介导生长板中软骨细胞和成骨细胞之间的交叉调节。
