Estrogen enhances alpha v beta 3 integrin expression by avian osteoclast precursors via stabilization of beta 3 integrin mRNA.
Although bone resorption is accelerated with menopause, the means by which diminished circulating 17 beta-estradiol (E2) promotes osteoclastic activity are unknown. We hypothesized that since the integrin alpha v beta 3 is essential to the resorptive process, reduced E2 levels may increase the integrin's expression by osteoclast precursors. Thus, avian osteoclast precursors (known to contain E2 receptors) were exposed +/- E2, surface iodinated, and lysed. The lysate was immunoprecipitated with an antibody recognizing the intact alpha v beta 3 heterodimer. We find E2 alone fails to impact on alpha v beta 3 expression. Most importantly, however, picomolar (i.e. post-menopausal), but not nanomolar (i.e. premenopausal) concentrations of E2, when added in conjunction with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], enhance alpha v beta 3 expression on the plasma membrane of avian osteoclast precursors relative to 1,25(OH)2D3 alone. Induction of alpha v beta 3 by picomolar levels of E2 is dose-dependent, maximizing at 10(-11)-10(-12) M, wherein the sex steroid enhances 1,25-(OH)2-D3-stimulated integrin expression approximately 2.5-fold. Northern analysis reveals that beta 3 mRNA levels parallel those of alpha v beta 3. E2 (10(-12) M) increases expression of beta 3 mRNA induced by a range of 1,25-(OH)2D3 concentrations extending from 10(-10) m-10(-8) M. The E2 + 1,25-(OH)2D3 additive effect on beta 3 mRNA appears as early as 1 day of treatment and progresses for at least 3 days. Consistent with evidence that the beta 3 subunit regulates heterodimer expression, the sex steroid does not impact alpha v mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015152:Blotting, Northern; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D004967:Estrogens / Q000494:pharmacology*; D039661:Integrin beta3; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D019030:Receptors, Vitronectin / Q000096:biosynthesis*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D015703:Antigens, CD; D004967:Estrogens; D039661:Integrin beta3; D012333:RNA, Messenger; D019030:Receptors, Vitronectin