{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T19:55:26Z","timestamp":1760385326440},"reference-count":56,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We have examined several analogs of 1\u03b1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in an animal model of osteoporosis (ovariectomized rats) to identify a compound with a greater therapeutic range than 1,25-(OH)2D3 for treatment of this bone disease. Here, we report that one analog, Ro-26-9228, had a bone-protecting effect but did not induce hypercalcemia at a wide concentration range. Analysis of biochemical markers and the bone histomorphometry of analog-treated rats suggested that Ro-26-9228 acted by inhibiting bone resorption and increasing the number of differentiated osteoblasts. To determine the basis for the segregation between hypercalcemia and bone-protecting action, we examined gene expression in tissues that regulate calcium homeostasis. We found that 1,25-(OH)2D3 induced 24-hydroxylase mRNA expression in the duodena of ovariectomized rats, but Ro-26-9228 did not. Furthermore, in the duodena of intact animals, 1,25-(OH)2D3 induced a significant increase in calbindin D 9K and plasma membrane calcium pump 1 mRNAs, but Ro-26-9228 had no effect on these mRNAs. On the other hand, the osteoblast-specific gene products osteocalcin and osteopontin were significantly up-regulated in trabecular bone by both the natural hormone and Ro-26-9228. Further investigation of gene-regulatory events in trabecular bone revealed that both 1,25-(OH)2D3 and Ro-26-9228 up-regulated TGF \u03b21 and \u03b22 mRNAs. We concluded that the unique properties of Ro-26-9228 include preferential gene regulation in osteoblasts over duodenum and effective induction of growth factors in bone.<\/jats:p>","DOI":"10.1210\/endo.143.5.8777","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T16:12:05Z","timestamp":1389197525000},"page":"1625-1636","source":"Crossref","is-referenced-by-count":26,"title":["Cellular and Molecular Events Associated with the Bone-Protecting Activity of the Noncalcemic Vitamin D Analog Ro-26-9228 in Osteopenic Rats"],"prefix":"10.1210","volume":"143","author":[{"given":"Sara","family":"Peleg","sequence":"first","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas, M. D. 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