1,25-Dihydroxyvitamin D3 transcriptionally activates the beta 3-integrin subunit gene in avian osteoclast precursors.
Osteoclasts are polykaryons and the principal, if not exclusive, resorptive cell of bone. They are members of the monocyte/macrophage family whose precursors differentiate under the influence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Bone resorption is dependent on osteoclast-bone attachment, and we have shown that the integrin alpha v beta 3 is critical to the resorptive process. Thus, we asked whether 1,25-(OH)2D3 enhances the expression of alpha v beta 3 on the surface of osteoclast precursors and if the steroid modulates expression of the beta 3-integrin subunit. We found that 1,25-(OH)2D3 promotes the plasma membrane appearance of alpha v beta 3 on avian bone marrow-derived osteoclast precursors and does so at physiological concentrations (10(-11) M) of the steroid. The effect is time dependent, appearing within 1 day of treatment. A full-length avian cDNA was cloned to explore the molecular mechanisms of beta 3 expression. The deduced amino acid sequence of the cDNA is 81% identical and 89% similar to that of human beta 3. Northern analysis demonstrates that beta 3 mRNA levels in vitamin D-treated osteoclast precursors mirror protein expression. Nuclear run-on experiments document the transcriptional nature of the event.
Mimura
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H
Department of Pathology and Laboratory Medicine, Jewish Hospital at Washington University Medical Center, St. Louis, Missouri 63110.
Cao
X
X
Ross
F P
FP
Chiba
M
M
Teitelbaum
S L
SL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D002645:Chickens; D003001:Cloning, Molecular; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D039661:Integrin beta3; D016023:Integrins / Q000235:genetics*; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D039661:Integrin beta3; D016023:Integrins; D002117:Calcitriol