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Osteoclasts Lacking Rac2 Have Defective Chemotaxis and Resorptive Activity

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Abstract

The role of the small Rho GTPase Rac2 in mature osteoclasts has not been extensively studied. Rac2−/− mice are of normal size and have normal tooth eruption. However, femoral cortical thickness was significantly greater in Rac2−/− compared to wild-type mice, while percent cortical porosity was lower. As assessed by histomorphometry, trabecular bone mass was significantly higher in male Rac2−/− than wild-type animals, although trabecular bone mass was similar when data from male and female animals were combined. There were no significant differences in the number of osteoblasts per bone surface; however, the number of osteoclasts per total bone area tended to be higher in Rac2−/− mice and was significantly higher in male Rac2−/− mice. In the aggregate, these data suggested a defect in osteoclast function and, consistent with that, rates of bone resorption were significantly reduced in Rac2−/− osteoclasts. In addition, Rac2−/− osteoclasts had a significantly delayed spreading response to treatment with CSF1 for 15 min. Phalloidin staining showed areas of abnormal actin accumulation and impaired actin ring formation in Rac2−/− osteoclasts. Finally, Rac2−/− osteoclasts showed a marked defect in chemotaxis toward a point source of CSF1, with a dramatic reduction in migratory rate. Together, these findings indicate an important role for Rac2 in mature osteoclasts.

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Acknowledgment

This work was supported by NIH grants DE12459 and DK45228 and by the Yale Core Center for Musculoskeletal Disorders, which is supported by a P30 Core Center Award from NIAMS (AR46032).

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Correspondence to Karl Insogna.

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Itokowa, T., Zhu, Ml., Troiano, N. et al. Osteoclasts Lacking Rac2 Have Defective Chemotaxis and Resorptive Activity. Calcif Tissue Int 88, 75–86 (2011). https://doi.org/10.1007/s00223-010-9435-3

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  • DOI: https://doi.org/10.1007/s00223-010-9435-3

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