Sanyal Arunik, Oursler Merry Jo, Clemens Victoria R, Fukumoto Takumi, Fitzsimmons James S, O'Driscoll Shawn W
Department of Orthopedics, Cartilage and Connective Tissue Research Laboratory, Mayo Clinic and Majo Foundation, Rochester, MN 55905, USA.
J Orthop Res. 2002 Jan;20(1):58-65. doi: 10.1016/S0736-0266(01)00078-X.
Articular cartilage has a limited ability to repair itself. Periosteal grafts have chondrogenic potential and are used clinically to repair defects in articular cartilage. An organ culture model system for in vitro rabbit periosteal chondrogenesis has been established to study the molecular events of periosteal chondrogenesis in vitro. In this model, bone morphogenetic protein-2 (BMP2) mRNA expression was found to be upregulated in the first 12 h. BMPs usually transduce their signals through a receptor complex that includes type II and either type IA or type IB BMP receptors. Receptors IA and IB play distinct roles during limb development. We have examined the temporal expression patterns for the mRNAs of these receptors using our experimental model. The mRNA expression patterns of these three BMP receptors differed from one another in periosteal explants during chondrogenesis. When these explants were cultured under chondrogenic conditions (agarose suspension with TGF-beta1 added to the media for the first 2 days), the expression of BMPRII mRNA and that of BMPRIA mRNA varied only slightly and persisted over a long time. In contrast, the expression of BMPRIB mRNAwas upregulated within 12 h, peaked at day 5, and fell to a level that was barely detected beyond day 21. Moreover, the expression of BMPRIB mRNA preceded that of collagen type IIB mRNAs, a marker for matrix-depositing chondrocytes. These data support a role for coordinate expression of BMP2 and its receptors early during periosteal chondrogenesis.
关节软骨自我修复能力有限。骨膜移植物具有软骨形成潜能,临床上用于修复关节软骨缺损。已建立一种体外兔骨膜软骨形成的器官培养模型系统,以研究体外骨膜软骨形成的分子事件。在该模型中,发现骨形态发生蛋白-2(BMP2)mRNA表达在前12小时上调。骨形态发生蛋白通常通过包含II型以及IA型或IB型骨形态发生蛋白受体的受体复合物转导其信号。受体IA和IB在肢体发育过程中发挥不同作用。我们使用我们的实验模型研究了这些受体mRNA的时间表达模式。在软骨形成过程中,这三种骨形态发生蛋白受体的mRNA表达模式在骨膜外植体中彼此不同。当这些外植体在软骨形成条件下培养(最初2天在培养基中添加TGF-β1的琼脂糖悬浮液)时,BMPRII mRNA和BMPRIA mRNA的表达仅略有变化,并长时间持续。相反,BMPRIB mRNA的表达在12小时内上调,在第5天达到峰值,并在第21天之后降至几乎检测不到的水平。此外,BMPRIB mRNA的表达先于IIB型胶原mRNA(基质沉积软骨细胞的标志物)的表达。这些数据支持骨膜软骨形成早期BMP2及其受体协调表达的作用。