{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T19:59:49Z","timestamp":1762459189855,"version":"build-2065373602"},"reference-count":65,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T00:00:00Z","timestamp":1409184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:p>\n                    Polymorphisms of the P2X7 receptor have been associated with increased risk of fractures in postmenopausal women. Although both osteoblasts and osteoclasts express P2X7 receptors, their function in osteogenesis remains controversial. Here, we investigated the role of the P2X7 receptor on osteogenic differentiation and mineralization of bone marrow mesenchymal stem cell (BMSC) cultures from postmenopausal women (age 71 \u00b1 3 yr,\n                    <jats:italic>n<\/jats:italic>\n                    =18). We focused on the mechanisms related to intracellular [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    oscillations and plasma membrane\u2010dynamics. ATP, and the P2X7 agonist BzATP (100 \u03bcM), increased [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    in parallel to the formation of membrane pores permeable to TO\u2010PRO\u20103 dye uptake. ATP and BzATP elicited reversible membrane blebs (zeiosis) in 38 \u00b1 1 and 70 \u00b1 1% of the cells, respectively. P2X7\u2010induced zeiosis was Ca\n                    <jats:sup>2+<\/jats:sup>\n                    independent, but involved phospholipase C, protein kinase C, and Rho\u2010kinase activation. BzATP (100 \u03bcM) progressively increased the expression of Runx\u20102 and Osterix transcription factors by 452 and 226% (at d 21), respectively, alkaline phosphatase activity by 88% (at d 28), and mineralization by 329% (at d 43) of BMSC cultures in a Rho\u2010kinase\u2010dependent manner. In summary, reversible plasma membrane zeiosis involving cytoskeleton rearrangements due to activation of the P2X7\u2010Rho\u2010kinase axis promotes osteogenic differentiation and mineralization of BMSCs, thus providing new therapeutic targets for postmenopausal bone loss.\u2014Noronha\u2010Matos, J. B., Coimbra, J., S\u00e1\u2010e\u2010Sousa, A., Rocha, R., Marinhas, J., Freitas, R., Guerra\u2010Gomes, S., Ferreirinha, F., Costa, M. A., Correia\u2010de\u2010S\u00e1, P., P2X7\u2010induced zeiosis promotes osteogenic differentiation and mineralization of postmenopausal bone marrow\u2010derived mesenchymal stem cells FASEB J. 28, 5208\u20135222 (2014).\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.14-257923","type":"journal-article","created":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T22:56:28Z","timestamp":1409266588000},"page":"5208-5222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["P2X7\u2010induced zeiosis promotes osteogenic differentiation and mineralization of postmenopausal bone marrow\u2010derived mesenchymal stem cells"],"prefix":"10.1096","volume":"28","author":[{"given":"Jos\u00e9 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