{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:44:52Z","timestamp":1791276292432,"version":"4.1.0"},"reference-count":54,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2000,5,1]]},"abstract":"<jats:p>Osteoblasts subjected to fluid shear increase the expression of the early response gene, c- fos, and the inducible isoform of cyclooxygenase, COX-2, two proteins linked to the anabolic response of bone to mechanical stimulation, in vivo. These increases in gene expression are dependent on shear-induced actin stress fiber formation. Here, we demonstrate that MC3T3-E1 osteoblast-like cells respond to shear with a rapid increase in intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) that we postulate is important to subsequent cellular responses to shear. To test this hypothesis, MC3T3-E1 cells were grown on glass slides coated with fibronectin and subjected to laminar fluid flow (12 dyn\/cm<jats:sup>2<\/jats:sup>). Before application of shear, cells were treated with two Ca<jats:sup>2+<\/jats:sup>channel inhibitors or various blockers of intracellular Ca<jats:sup>2+<\/jats:sup>release for 0.5\u20131 h. Although gadolinium, a mechanosensitive channel blocker, significantly reduced the [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>response, neither gadolinium nor nifedipine, an L-type channel Ca<jats:sup>2+<\/jats:sup>channel blocker, were able to block shear-induced stress fiber formation and increase in c-fos and COX-2 in MC3T3-E1 cells. However, 1,2-bis(2-aminophenoxy)ethane- N, N, N\u2032, N\u2032-tetraacetic acid-AM, an intracellular Ca<jats:sup>2+<\/jats:sup>chelator, or thapsigargin, which empties intracellular Ca<jats:sup>2+<\/jats:sup>stores, completely inhibited stress fiber formation and c-fos\/COX-2 production in sheared osteoblasts. Neomycin or U-73122 inhibition of phospholipase C, which mediates d- myo-inositol 1,4,5-trisphosphate (IP<jats:sub>3<\/jats:sub>)-induced intracellular Ca<jats:sup>2+<\/jats:sup>release, also completely suppressed actin reorganization and c-fos\/COX-2 production. Pretreatment of MC3T3-E1 cells with U-73343, the inactive isoform of U-73122, did not inhibit these shear-induced responses. These results suggest that IP<jats:sub>3<\/jats:sub>-mediated intracellular Ca<jats:sup>2+<\/jats:sup>release is required for modulating flow-induced responses in MC3T3-E1 cells.<\/jats:p>","DOI":"10.1152\/ajpcell.2000.278.5.c989","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:54:13Z","timestamp":1514156053000},"page":"C989-C997","source":"Crossref","is-referenced-by-count":247,"title":["Ca<sup>2+<\/sup>regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts"],"prefix":"10.1152","volume":"278","author":[{"given":"Neal X.","family":"Chen","sequence":"first","affiliation":[{"name":"Departments of Anatomy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly D.","family":"Ryder","sequence":"additional","affiliation":[{"name":"Physiology and Biophysics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick 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