{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T04:05:07Z","timestamp":1769227507228,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mechanical stress determines bone mass and structure. It is not known whether mechanical loading affects expression of bone regulatory genes in a combined deficiency of estrogen and vitamin D. We studied the effect of mechanical loading on the messenger RNA (mRNA) expression of bone regulatory genes during vitamin D and\/or estrogen deficiency. We performed a single bout in vivo axial loading with 14\u2009N peak load, 2\u2009Hz frequency and 360 cycles in right ulnae of nineteen weeks old female control Wistar rats with or without ovariectomy (OVX), vitamin D deficiency and the combination of OVX and vitamin D deficiency (N\u2009=\u200910\/group). Total bone RNA was isolated 6\u2009hours after loading, and mRNA expression was detected of <jats:italic>Mepe, Fgf23, Dmp1, Phex, Sost, Col1a1, Cyp27b1, Vdr<\/jats:italic>, and <jats:italic>Esr1<\/jats:italic>. Serum levels of 25(OH)D, 1,25(OH)<jats:sub>2<\/jats:sub>D and estradiol were also measured at this time point. The effect of loading, vitamin D and estrogen deficiency and their interaction on bone gene expression was tested using a mixed effect model analysis. Mechanical loading significantly increased the mRNA expression of <jats:italic>Mepe<\/jats:italic>, and <jats:italic>Sost<\/jats:italic>, whereas it decreased the mRNA expression of <jats:italic>Fgf23<\/jats:italic> and <jats:italic>Esr1<\/jats:italic>. Mechanical loading showed a significant interaction with vitamin D deficiency with regard to mRNA expression of <jats:italic>Vdr<\/jats:italic> and <jats:italic>Esr1<\/jats:italic>. Mechanical loading affected gene expression of <jats:italic>Mepe, Fgf23, Sost<\/jats:italic>, and <jats:italic>Esr1<\/jats:italic> independently of vitamin D or estrogen, indicating that mechanical loading may affect bone turnover even during vitamin D deficiency and after menopause.<\/jats:p>","DOI":"10.1002\/jor.24775","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T14:11:29Z","timestamp":1591971089000},"page":"42-52","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mechanical stress regulates bone regulatory gene expression independent of estrogen and vitamin D deficiency in rats"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4241-6621","authenticated-orcid":false,"given":"Ashwini Kumar","family":"Nepal","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry,\u00a0Amsterdam UMC Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huib W.","family":"van Essen","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry,\u00a0Amsterdam UMC Vrije Universiteit Amsterdam, Amsterdam Movement Sciences  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert J.","family":"van der Veen","sequence":"additional","affiliation":[{"name":"Department of Physics and Medical Technology,\u00a0Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wessel N.","family":"van Wieringen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics,\u00a0Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Mathematics Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea W. 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