Osteoclasts lacking Rac2 have defective chemotaxis and resorptive activity.
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.
Department of Medicine, Yale School of Medicine, 333 Cedar St., TAC S133, New Haven, CT 06520-8020, USA. itok81@aol.com
Takashi
T
Itokowa
Mei-ling
ML
Zhu
Nancy
N
Troiano
Jessica
J
Bian
Tustomu
T
Kawano
Karl
K
Insogna
D000818:Animals; D015519:Bone Density / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics*; D001842:Bone and Bones / Q000033:anatomy & histology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics*; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000235:genetics; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000097766:RAC2 GTP-Binding Protein
D016173:Macrophage Colony-Stimulating Factor; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein