1,25-Dihydroxyvitamin D3 transcriptionally activates the β3-integrin subunit gene in avian osteoclast precursors

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 (10-11 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 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.