1,25-DIHYDROXYVITAMIN D-3 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 D-3 [1,25-(OH)(2)D-3]. 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)(2)D-3 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)(2)D-3 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 ps 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.