Granulocyte macrophage-colony stimulating factor reciprocally regulates α(v)-associated integrins on murine osteoclast precursors

The integrins α(v)/β₃ and α(v)β₃ are expressed reciprocally during murine osteoclastogenesis in vitro. Specifically, immature osteoclast precursors, in the form of bone marrow macrophages, contain exclusively α(v)/β₅, surface expression of which declines with commitment to the osteoclast phenotype, while levels of α(v)/β₃ increase concomitantly. The distinct functional significance of α(v)/β₅ is underscored by the integrin's capacity, unlike α(v)β₃, to mediate both attachment and spreading on ligand, of marrow macrophages, suggesting α(v)β₅ negotiates initial recognition, by osteoclast precursors, of bone matrix. Northern analysis demonstrates changes in the two β-subunits, and not α(v), are responsible for these alterations. Treatment of early precursors with granulocyte-macrophage colony stimulating factor (GM-CSF) leads to alterations in β₃ and β₅ mRNA and α(v)β₅ and α(v)β₃, paralleling those occurring during osteoclastogenesis. Nuclear run-on and message stability studies demonstrate that while GM-CSF treatment of precursors alters β₅ transcriptionally, the changes in β₃ arise from prolonged mRNA t(1/2). Similar to GM-CSF treatment, the rate of β₅ transcription falls during authentic osteoclastogenesis. In contrast to cytokine-induced α(v)β₃, however, that attending osteoclastogenesis reflects accelerated transcription of the β₃-subunit. Thus, while GM-CSF may participate in modulation of α(v)β₅ during osteoclast differentiation, signals other than those derived from the cytokine must regulate expression of α(v)β₃.