title: Mechanotransduction in stretched osteocytes--temporal expression of immediate early and other genes.
abstract: 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.
authors.affiliation: Department of Oral Biochemistry, Kanagawa Dental College, Yokosuka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawata
authors.forename: Y
authors.initials: Y
authors.lastname: Mikuni-Takagaki
mesh_terms: D000818:Animals; D001483:Base Sequence; D001696:Biomechanical Phenomena; D051546:Cyclooxygenase 2; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D017781:Genes, Immediate-Early; D016762:Genes, fos; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D015675:Osteocalcin / Q000235:genetics; D010011:Osteocytes / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D012333:RNA, Messenger; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases