MECHANOTRANSDUCTION IN STRETCHED OSTEOCYTES - TEMPORAL EXPRESSION OF IMMEDIATE-EARLY AND OTHER GENES

Osteocytes, dendritic bone cells, transduce signals of mechanical load ing that results in bone formation. We have reported in stretched prim ary osteocytes that the cAMP level, IGF-I and osteocalcin protein leve ls were elevated (Endocrinology 137:2028, 1996). Here we report that s tretching induces the expression of immediate early genes, c-fos and C OX-2; inducive cyclooxygenase gene. Compared to c-fos, COX-2 as well a s IGF-I and osteocalcin mRNA appeared in a biphasic manner; second pea ks at 8 (COX-2) or 24 hrs (IGF-I and osteocalcin) later. Furthermore, these second peaks are abolished by including NS398, a specific inhibi tor of the inducive cyclooxygenase, during the 3-hr stretching. A sequ ence that the calcium influx activates PkA which, in turn, activates c -fos and COX-2 transcription resulting in the production of proteins s uch as IGF-I and osteocalcin. A long-lasting effect of mechanical load ing in vivo can be explained from the secondary anabolic reaction we o bserved through the upregulated COX-2 mRNA. (C) 1998 Academic Press.