Machwate M, Jullienne A, Moukhtar M, Marie P J
INSERM Unité 349, Cell and Molecular Biology of Bone and Cartilage, Lariboisiere Hospital, Paris, France.
J Cell Biochem. 1995 Jan;57(1):62-70. doi: 10.1002/jcb.240570108.
To delineate the implication of c-fos protooncogenic in the osteogenie process, we have investigated the temporal pattern of c-fos mRNA expression in fetal and neonatal rat bone during intramembranous and endochondral bone formation. Northern blot analysis of mRNA extracted from calvaria and femur showed that expression of c-fos, Histone H4, and osteocalcin mRNAs followed a temporal sequence during bone development. The levels of histone H4 mRNA, a marker of cell proliferation, were high at early stages of fetal development of calvaria and femur, and decreased until birth. In both the postnatal calvaria and femur, c-fos mRNA levels increased transiently at birth and preceded a rise in osteocalcin transcripts, a marker of the mature osteoblast phenotype. The immunohistochemical analysis showed that c-Fos protein was expressed in osteoprogenitor cells in the perichondrium and periosteum, and not in mature osteoblasts which expressed markers of differentiated osteoblasts such as type-I collagen, bone sialoprotein, and osteocalcin. Thus, the transient c-fos proto-oncogene expression during the postnatal life that precedes the osteocalcin expression may be involved in the transition from the precursor state to mature osteoblasts. These results suggest that c-fos proto-oncogene may play an important role in osteogenesis during rat postnatal life.
为了阐明c-fos原癌基因在成骨过程中的作用，我们研究了在膜内成骨和软骨内成骨过程中，胎鼠和新生鼠骨骼中c-fos mRNA表达的时间模式。对从颅骨和股骨中提取的mRNA进行Northern印迹分析表明，在骨骼发育过程中，c-fos、组蛋白H4和骨钙素mRNA的表达遵循时间顺序。组蛋白H4 mRNA水平作为细胞增殖的标志物，在颅骨和股骨胎儿发育早期较高，出生前下降。在出生后的颅骨和股骨中，c-fos mRNA水平在出生时短暂升高，并先于骨钙素转录本的升高，骨钙素是成熟成骨细胞表型的标志物。免疫组织化学分析表明，c-Fos蛋白在软骨膜和骨膜中的骨祖细胞中表达，而在表达I型胶原、骨唾液蛋白和骨钙素等成骨细胞分化标志物的成熟成骨细胞中不表达。因此，出生后在骨钙素表达之前短暂的c-fos原癌基因表达可能参与了从前体状态到成熟成骨细胞的转变。这些结果表明，c-fos原癌基因可能在大鼠出生后的成骨过程中起重要作用。
