{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:15:53Z","timestamp":1793330153739,"version":"4.5.0"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2004,6,1]],"date-time":"2004-06-01T00:00:00Z","timestamp":1086048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Osteoblast-like cells in primary cultures derived from ER\u03b1\u2212\/\u2212 mice do not proliferate in response to mechanical strain, unlike those from their ER\u03b1+\/+ littermates. ER\u03b1\u2212\/\u2212 cells also lack strain-related NO production and responsiveness to IGFs. Proliferative responsiveness to strain is rescued by transfection with functional ER\u03b1. ER\u03b1 number or function in bone cells may limit bones' adaptability to mechanical loading.<\/jats:p>\n               <jats:p>Introduction: In vivo, bones' osteogenic response to mechanical loading involves proliferation of surface osteoblasts. This response is replicated in vitro and involves ERK-mediated activation of the estrogen receptor (ER) \u03b1 and upregulation of estrogen response element activity. This proliferative response can be blocked by selective estrogen receptor modulators and increased by transfection of additional ER\u03b1.<\/jats:p>\n               <jats:p>Materials and Methods: We have now investigated the mechanisms of ER involvement in osteoblast-like cells' early responses to strain by comparing the responses of primary cultures of these cells derived from homozygous ER\u03b1 knockout (ERKO) mice (ER\u03b1\u2212\/\u2212) with those from their wildtype (ER\u03b1+\/+) and heterozygous (ER\u03b1+\/\u2212) littermates and from ER\u03b2 knockout (BERKO) mice (ER\u03b2+\/+, ER\u03b2+\/\u2212, and ER\u03b2\u2212\/\u2212).<\/jats:p>\n               <jats:p>Results: Whereas ER\u03b1+\/+, ER\u03b1+\/\u2212, ER\u03b2+\/+, and ER\u03b2\u2212\/\u2212 cells proliferate in response to a single 10-minute period of cyclic strain, ER\u03b1\u2212\/\u2212 cells do not. Transfection of fully functional, but not mutant, ER\u03b1 rescues the proliferative response to strain in these cells. The strain-related response of ER\u03b1\u2212\/\u2212 cells is also deficient in that they show no increased activity of an AP-1 driven reporter vector and no strain-related increases in NO production. Their strain-related increase in prostacyclin production is retained. They proliferate in response to fibroblast growth factor-2 but not insulin-like growth factor (IGF)-I or IGF-II, showing the importance of ER\u03b1 in the IGF axis and the ability of ER\u03b1\u2212\/\u2212 cells to proliferate normally in response to a mitogenic stimulus that does not require functional ER\u03b1.<\/jats:p>\n               <jats:p>Conclusions: These data indicate ER\u03b1's obligatory involvement in a number of early responses to mechanical strain in osteoblast-like cells, including those that result in proliferation. They support the hypothesis that reduction in ER\u03b1 expression or activity after estrogen withdrawal results in a less osteogenic response to loading. This could be important in the etiology of postmenopausal osteoporosis.<\/jats:p>","DOI":"10.1359\/jbmr.2004.19.6.938","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T06:45:46Z","timestamp":1146120346000},"page":"938-946","source":"Crossref","is-referenced-by-count":80,"title":["Osteoblast-Like Cells From Estrogen Receptor \u03b1 Knockout Mice Have Deficient Responses to Mechanical Strain"],"prefix":"10.1093","volume":"19","author":[{"given":"Helen L","family":"Jessop","sequence":"first","affiliation":[{"name":"Department of Veterinary Basic Sciences, The Royal Veterinary College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary FL","family":"Suswillo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Basic Sciences, The Royal Veterinary College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon 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