Alan Tulay, Tufan A Cevik
Department of Histology and Embryology, Institute of Health Sciences, Pamukkale University, Denizli, Turkey.
J Cell Biochem. 2008 Sep 1;105(1):227-35. doi: 10.1002/jcb.21815.
AMDM, a form of osteochondrodysplasia, is due to the loss-of-function mutations in NPR-B gene. This study investigated the functional involvement of CNP-3, chick homolog of human CNP, and its receptor NPR-B in chondrogenesis utilizing the micromass culture of the chick limb mesenchymal cells. Results revealed CNP-3 and NPR-B expression in the chick limb bud making stage-specific peak levels first at Hamburger-Hamilton stage 23-24, and second at stage 30-31, corresponding to pre-chondrogenic mesenchymal condensation and initiation of chondrogenic maturation-hypertrophy in vivo, respectively. CNP-3 and NPR-B expression in vitro increased parallel to collagen type X expression, but not to that of collagen type II. Treatment of cultures with CNP significantly increased N-cadherin, and collagen type X expression, glycosaminoglycan synthesis and chondrogenesis. Collagen type II expression was not significantly affected. Thus, results implicated CNP-3/NPR-B signaling in pre-chondrogenic mesenchymal condensation, glycosaminoglycan synthesis and late differentiation of chondrocytes in the process of endochondral ossification.
AMDM是一种骨软骨发育不良，由NPR - B基因的功能丧失突变引起。本研究利用鸡胚肢体间充质细胞的微团培养，研究了人CNP的鸡同源物CNP - 3及其受体NPR - B在软骨形成中的功能作用。结果显示，在鸡胚肢体芽形成阶段，CNP - 3和NPR - B的表达分别在汉密尔顿-汉堡分期的第23 - 24阶段和第30 - 31阶段出现阶段特异性峰值水平，分别对应体内软骨前间充质凝聚和软骨形成成熟-肥大的起始阶段。体外培养时，CNP - 3和NPR - B的表达与X型胶原的表达平行增加，但与II型胶原的表达无关。用CNP处理培养物可显著增加N - 钙黏蛋白、X型胶原的表达、糖胺聚糖的合成及软骨形成。II型胶原的表达未受显著影响。因此，结果表明CNP - 3/NPR - B信号通路参与软骨内骨化过程中软骨前间充质凝聚、糖胺聚糖合成及软骨细胞的晚期分化。
