PTH/PTHrP receptor delays chondrocyte hypertrophy via both Runx2-dependent and -independent pathways
PTH/PTHrP receptor delays chondrocyte hypertrophy via both Runx2-dependent and -independent pathways
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DOI：
10.1016/j.ydbio.2005.12.044
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发表时间：
2006-04-01
影响因子：
2.7
通讯作者：
Kronenberg, HM
中科院分区：
文献类型：
--
作者：
Guo, J;Chung, UI;Kronenberg, HM
转录因子Runx 2促进软骨细胞肥大，而甲状旁腺相关蛋白（PTHrP）延迟这一过程。为了检查PTHrP是否通过Runx 2依赖性或非依赖性途径抑制软骨细胞肥大，使用来自野生型和Runx 2（-/-）小鼠的胚胎肢的骨分析Runx 2表达和软骨细胞分化。用PTH处理培养的雏形显著抑制肥大软骨细胞中Runx 2 mRNA水平。在来自Runx 2（-/-）和野生型胚胎的培养的软骨细胞中观察到PTH诱导的软骨细胞肥大延迟。在通过胶原蛋白2启动子驱动的转基因向软骨细胞中表达Runx 2的野生型和Runx 2（-/-）小鼠的肢体施用PTH后也观察到这种延迟。进一步探讨PTHrP的Runx 2依赖性和非依赖性作用。我们检查了PTHrP无效的同窝出生仔的胚胎胫骨和股骨。Runx 2或两种基因，Runx 2（-/-）股骨显示无血管浸润或软骨细胞表达X型胶原或骨桥蛋白mRNA。相反，Runx 2（-/-）/PTHrP（-/-）小鼠表现出有限的血管侵袭和一些软骨细胞表达胶原X或骨桥蛋白mRNA。在胫骨和股骨中，当与PTHrP（-/-）小鼠中的相同区域相比时，Runx 2（-/-）1 PTHrP（-/-）小鼠表现出增殖软骨细胞的扩展区域。这些数据表明，PTHrP诱导的迟发性肥大是由Runx 2依赖性和非依赖性机制介导的。(c)2006年爱思唯尔公司All rights reserved.
The transcription factor, Runx2, promotes chondrocyte hypertrophy, whereas parathyroid hormone-related protein (PTHrP) delays this process. To examine whether PTHrP Suppresses chondrocyte hypertrophy via Runx2-dependent or -independent pathways, Runx2 expression and chondrocyte differentiation were analyzed using bones from embryonic limbs of wild type and Runx2(-/-) mice. Treatment of cultured rudiments with PTH dramatically Suppresses Runx2 mRNA levels in hypertrophic chondrocytes. PTH-induced delay of chondrocyte hypertrophy was observed in cultured tibiae From both Runx2(-/-) and wild-type embryos. This delay was also seen after PTH administration to limbs from wild type and Runx2(-/-) mice expressing Runx2 in chondrocytes via a collagen 2 promoter-driven transgene. To further explore Runx2-dependent and -independent effects of PTHrP. we examined embryonic tibiae and femurs from littermates null for PTHrP. Runx2, or both genes, Runx2(-/-) femurs exhibited no vascular invasion or chondrocytes expressing collagen type X or osteopontin mRNA. In contrast, Runx2(-/-)/PTHrP(-/-) mice exhibited limited vascular invasion and some chondrocytes expressing collagen X or osteopontin mRNA. In both tibia and femur, Runx2(-/-)l PTHrP(-/-) mice exhibited expanded regions of proliferating chondrocytes when compared to the same regions in PTHrP(-/-) mice. These data indicate that the delayed hypertrophy induced by PTHrP is mediated by both Runx2-dependent and -independent mechanisms. (c) 2006 Elsevier Inc. All rights reserved.