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Granulocyte Macrophage-Colony Stimulating Factor Reciprocally Regulates _v-Associated Integrins on Murine Osteoclast Precursors

Department of Pathology Washington University School of Medicine St. Louis, Missouri 63110

The integrins _vß₅ and _vß₃ are expressed reciprocally during murine osteoclastogenesis in vitro. Specifically, immature osteoclast precursors, in the form of bone marrow macrophages, contain exclusively _vß₅, surface expression of which declines with commitment to the osteoclast phenotype, while levels of _vß₃ increase concomitantly. The distinct functional significance of _vß₅ is underscored by the integrin’s capacity, unlike _vß₃, to mediate both attachment and spreading on ligand, of marrow macrophages, suggesting _vß₅ negotiates initial recognition, by osteoclast precursors, of bone matrix. Northern analysis demonstrates changes in the two ß-subunits, and not _v, are responsible for these alterations. Treatment of early precursors with granulocyte-macrophage colony stimulating factor (GM-CSF) leads to alterations in ß₃ and ß₅ mRNA and _vß₅ and _vß₃, paralleling those occurring during osteoclastogenesis. Nuclear run-on and message stability studies demonstrate that while GM-CSF treatment of precursors alters ß₅ transcriptionally, the changes in ß₃ arise from prolonged mRNA t_1/2. Similar to GM-CSF treatment, the rate of ß₅ transcription falls during authentic osteoclastogenesis. In contrast to cytokine-induced _vß₃, however, that attending osteoclastogenesis reflects accelerated transcription of the ß₃-subunit. Thus, while GM-CSF may participate in modulation of _vß₅ during osteoclast differentiation, signals other than those derived from the cytokine must regulate expression of _vß₃.

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