Nakase T, Sugimoto M, Sato M, Kaneko M, Tomita T, Sugamoto K, Nomura S, Kitamura Y, Yoshikawa H, Yasui N, Yonenobu K, Ochi T
Department of Orthopaedic Surgery, Osaka University Medical School, Suita, Japan.
Acta Histochem. 1998 Jul;100(3):287-95. doi: 10.1016/S0065-1281(98)80015-9.
The process of cartilage-to-bone transition (CBT) is a key event for the achievement of rigid bone healing during fracture repair. Since mineralization of cartilaginous matrix is a prerequisite for the initiation of CBT, the genetic localization of mineralization-related bone matrix proteins in CBT was examined in this study. An in situ hybridization method used on decalcified sections with digoxigenin-11-UTP labelled probes identified the cellular localizations of these genes in CBT. Cessation of osteonectin mRNA together with induction of osteopontin mRNA in chondrocyte maturation was observed during the process of CBT in the fracture callus on day 12 after fracture; osteocalcin mRNA was absent in chondrocytes of the CBT area. Induction of osteopontin mRNA in maturated chondrocytes was followed by the expression of mRNAs for osteonectin, osteopontin and osteocalcin in osteogenic cells in the ossification front of CBT. The data suggest that the switch from osteonectin to osteopontin mRNA expression in chondrocyte maturation is one of the key events during CBT. Transcriptional disorders of the expression of these molecules may be linked to the failure of fracture repair, i.e. delayed or prevented hypertrophic osteosynthesis.
软骨向骨转换（CBT）过程是骨折修复过程中实现坚硬骨愈合的关键事件。由于软骨基质矿化是启动CBT的前提条件，本研究对CBT中矿化相关骨基质蛋白进行了基因定位研究。采用地高辛素-11-UTP标记探针的原位杂交方法在脱钙切片上确定了这些基因在CBT中的细胞定位。骨折后第12天，在骨折痂的CBT过程中观察到骨连接蛋白mRNA停止表达，同时在软骨细胞成熟过程中骨桥蛋白mRNA诱导表达；CBT区域的软骨细胞中未检测到骨钙素mRNA。成熟软骨细胞中骨桥蛋白mRNA诱导表达后，CBT骨化前沿的成骨细胞中骨连接蛋白、骨桥蛋白和骨钙素的mRNA表达。数据表明，软骨细胞成熟过程中从骨连接蛋白到骨桥蛋白mRNA表达的转变是CBT过程中的关键事件之一。这些分子表达的转录紊乱可能与骨折修复失败有关，即延迟或阻止肥大性骨合成。
