Kawata A, Mikuni-Takagaki Y
Department of Oral Biochemistry, Kanagawa Dental College, Yokosuka, Japan.
Biochem Biophys Res Commun. 1998 May 19;246(2):404-8. doi: 10.1006/bbrc.1998.8632.
Osteocytes, dendritic bone cells, transduce signals of mechanical loading that results in bone formation. We have reported in stretched primary osteocytes that the cAMP level, IGF-I and osteocalcin protein levels were elevated (Endocrinology 137:2028, 1996). Here we report that stretching induces the expression of immediate early genes, c-fos, and COX-2; inducive cyclooxygenase gene. Compared to c-fos, COX-2 as well as IGF-I and osteocalcin mRNA appeared in a biphasic manner; second peaks at 8 (COX-2) or 24 hrs (IGF-I and osteocalcin) later. Furthermore, these second peaks are abolished by including NS398, a specific inhibitor of the inducive cyclooxygenase, during the 3-hr stretching. A sequence that the calcium influx activates PkA which, in turn, activates c-fos and COX-2 transcription resulting in the production of proteins such as IGF-I and osteocalcin. A long-lasting effect of mechanical loading in vivo can be explained from the secondary anabolic reaction we observed through the upregulated COX-2 mRNA.
