{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T07:56:39Z","timestamp":1784447799122,"version":"3.55.0"},"reference-count":53,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,2,1]]},"abstract":"<jats:p>Rosiglitazone (Rosi) belongs to the class of thiazolidinediones (TZDs) that are ligands for peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3). Stimulation of PPAR\u03b3 suppresses bone formation and enhances marrow adipogenesis. We hypothesized that activation of PPAR\u03b3 down-regulates components of the IGF regulatory system, leading to impaired osteoblast function. Rosi treatment (1 \u03bcm) of a marrow stromal cell line (UAMS-33) transfected with empty vector (U-33\/c) or with PPAR\u03b32 (U-33\/\u03b32) were analyzed by microarray. Rosi reduced IGF-I, IGF-II, IGFBP-4, and the type I and II IGF receptor (IGF1R and IGF2R) expression at 72 h in U-33\/\u03b32 compared with U-33\/c cells (P &amp;lt; 0.01); these findings were confirmed by RT-PCR. Rosi reduced secreted IGF-I from U-33\/\u03b32 cells by 75% (P &amp;lt; 0.05). Primary marrow stromal cells (MSCs) extracted from adult (8 months) and old (24 months) C57BL\/6J (B6) mice were treated with Rosi (1 \u03bcm) for 48 h. IGF-I, IGFBP-4, and IGF1R transcripts were reduced in Rosi-treated MSCs compared with vehicle (P &amp;lt; 0.01) and secreted IGF-I was also suppressed (P &amp;lt; 0.05). B6 mice treated with Rosi (20 mg\/kg\u00b7d) for short duration (i.e. 4 d), and long term (i.e. 7 wk) had reduced serum IGF-I; this was accompanied by markedly suppressed IGF-I transcripts in the liver and peripheral fat of treated animals. To determine whether Rosi affected circulating IGF-I in humans, we measured serum IGF-I, IGFBP-2, and IGFBP-3 at four time points in 50 postmenopausal women randomized to either Rosi (8 mg\/d) or placebo. Rosi-treated subjects had significantly lower IGF-I at 8 wk than baseline (\u221225%, P &amp;lt; 0.05), and at 16 wk their levels were reduced 14% vs. placebo (P = 0.15). We conclude that Rosi suppresses IGF-I expression in bone and liver; these changes could affect skeletal acquisition through endocrine and paracrine pathways.<\/jats:p>","DOI":"10.1210\/en.2006-1121","type":"journal-article","created":{"date-parts":[[2006,11,23]],"date-time":"2006-11-23T01:54:37Z","timestamp":1164246877000},"page":"903-911","source":"Crossref","is-referenced-by-count":122,"title":["Activation of Peroxisome Proliferator-Activated Receptor \u03b3 (PPAR\u03b3) by Rosiglitazone Suppresses Components of the Insulin-Like Growth Factor Regulatory System in Vitro and in Vivo"],"prefix":"10.1210","volume":"148","author":[{"given":"B.","family":"Lecka-Czernik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ackert-Bicknell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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