Granulocyte macrophage-colony stimulating factor reciprocally regulates αv-associated integrins on murine osteoclast precursors

The integrins alpha(v)beta(5) and alpha(v)beta(3) are expressed reciprocally during murine osteoclastogenesis in vitro. Specifically, immature osteoclast precursors, in the form of bone marrow macrophages, contain exclusively alpha(v)beta(5), surface expression of which declines with commitment to the osteoclast phenotype, while levels of alpha(v)beta(3) increase concomitantly. The distinct functional significance of alpha(v)beta(5) is underscored by the integrin's capacity, unlike alpha(v)beta(3), to mediate both attachment and spreading on ligand, of marrow macrophages, suggesting alpha(v)beta(3), negotiates initial recognition, by osteoclast precursors, of bone matrix, Northern analysis demonstrates changes in the two beta-subunits, and not alpha(v), are responsible for these alterations. Treatment of early precursors with granulocyte-macrophage colony stimulating factor (GM-CSF) leads to alterations in beta(3) and beta(5) mRNA and alpha(v)beta(5) and alpha(v)beta(3), paralleling those occurring during osteoclastogenesis. Nuclear run-on and message stability studies demonstrate that while GM-CSF treatment of precursors alters beta(5) transcriptionally, the changes in beta(3) arise from prolonged mRNA t(1/2). Similar to GM-CSF treatment, the rate of beta(5) transcription falls during authentic osteoclastogenesis. In contrast to cytokine-induced alpha(v)beta(3), however, that attending osteoclastogenesis reflects accelerated transcription of the beta(3)-subunit, Thus, while GM-CSF may participate in modulation of alpha(v)beta(5) during osteoclast differentiation, signals other than those derived from the cytokine must regulate expression of alpha(v)beta(3).