1, 25-dihydroxyvitamin d3 transcriptionally activates the ² 3-integrin subunit gene in avian osteoclast precursors

Hirohide Mimura, Xu Cao, F. Patrick Ross, Mirei Chiba, Steven L. Teitelbaum

Research output: Contribution to journalArticle

Abstract

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 α v β3 is critical to the resorptive process. Thus, we asked whether 1, 25-(OH)2D3 enhances the expression of α v β3 on the surface of osteoclast precursors and if the steroid modulates expression of the β3-integrin subunit. We found that 1, 25-(OH)2D3 promotes the plasma membrane appearance of α v β3 on avian bone marrow-derived osteoclast precursors and does so at physiological concentrations (10-11M) 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 β3 expression. The deduced amino acid sequence of the cDNA is 81% identical and 89% similar to that of human β3. Northern analysis demonstrates that β3 mRNA levels in vitamin D-treated osteoclast precursors mirror protein expression. Nuclear run-on experiments document the transcriptional nature of the event.

Original languageEnglish (US)
Pages (from-to)1061-1066
Number of pages6
JournalEndocrinology
Volume134
Issue number3
DOIs
StatePublished - Apr 1994
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Endocrinology

Cite this