1, 25-dihydroxyvitamin d3 transcriptionally activates the ² 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 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.