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How\n                    <jats:italic>in situ<\/jats:italic>\n                    osteocytes respond to mechanical stimuli is still unclear because of technical difficulties.\n                    <jats:italic>In vitro<\/jats:italic>\n                    studies have shown that osteocytes exhibited unique calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) oscillations to fluid shear. However, whether this mechanotransduction phenomenon holds for\n                    <jats:italic>in situ<\/jats:italic>\n                    osteocytes embedded within a mineralized bone matrix under dynamic loading remains unknown. Using a novel synchronized loading\/imaging technique, we successfully visualized in real time and quantified Ca\n                    <jats:sup>2+<\/jats:sup>\n                    responses in osteocytes and bone surface cells\n                    <jats:italic>in situ<\/jats:italic>\n                    under controlled dynamic loading on intact mouse tibia. The resultant fluid\u2010induced shear stress on the osteocyte in the lacunocanalicular system (LCS) was also quantified. Osteocytes, but not surface cells, displayed repetitive Ca\n                    <jats:sup>2+<\/jats:sup>\n                    spikes in response to dynamic loading, with spike frequency and magnitude dependent on load magnitude, tissue strain, and shear stress in the LCS. The Ca\n                    <jats:sup>2+<\/jats:sup>\n                    oscillations were significantly reduced by endoplasmic reticulum (ER) depletion and P\n                    <jats:sub>2<\/jats:sub>\n                    purinergic receptor (P\n                    <jats:sub>2<\/jats:sub>\n                    R)\/phospholipase C (PLC) inhibition. This study provides direct evidence that osteocytes respond to\n                    <jats:italic>in situ<\/jats:italic>\n                    mechanical loading by Ca\n                    <jats:sup>2+<\/jats:sup>\n                    oscillations, which are dependent on the P\n                    <jats:sub>2<\/jats:sub>\n                    R\/PLC\/inositol trisphosphate\/ER pathway. This study develops a novel approach in skeletal mechanobiology and also advances our fundamental knowledge of bone mechanotransduction.\u2014Jing, D., Baik, A. D., Lu, X. L., Zhou, B., Lai, X., Wang, L., Luo, E., Guo, X. E.\n                    <jats:italic>In situ<\/jats:italic>\n                    intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 28\u20131582 (1592).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-237578","type":"journal-article","created":{"date-parts":[[2013,12,17]],"date-time":"2013-12-17T23:18:50Z","timestamp":1387322330000},"page":"1582-1592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["<i>In situ<\/i>\n                    intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading"],"prefix":"10.1096","volume":"28","author":[{"given":"Da","family":"Jing","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Fourth Military Medical University Xi'an Shaanxi China"},{"name":"Bone Bioengineering Laboratory, Department of Biomedical Engineering Columbia University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Baik","sequence":"additional","affiliation":[{"name":"Bone Bioengineering Laboratory, Department of Biomedical Engineering Columbia University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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