The In vivo effects of Rac1 and Rac2 on Bone Quality and Aging

Introduction: The Rho family of small GTPases, including Rac1 and Rac2, are key regulators of osteoclast differentiation and function; however, little is known about their roles in bone quality and aging. Methods: Male four and nine month old mice (n=10) with Rac1, Rac2 or both (DKO) isoforms deleted in osteoclast precursors were assessed using dual energy x-ray absorptiometry (DXA), scanning electron microscopy (SEM), micro computed tomography (microCT), compression, torsion and three-point bending testing, back scattered electron microscopy (BSE), Goldner’s trichrome and TRAP staining. Results: All Rac null mice demonstrated decreased cortical structural properties and improved trabecular architecture. With age, Rac null mice demonstrated the ability to attenuate age-related bone loss. Conclusions: Using an in vivo model with Rac1, Rac2 or both Rac isoforms deleted in osteoclasts, our findings demonstrate the deletion of Rac1 and Rac2 compromised cortical bone while improving trabecular bone properties and attenuated age-related bone loss.MAS