Opposing roles of hematopoietic-specific small GTPase Rac2 and the guanine nucleotide exchange factor Vav1 in osteoclast differentiation.

ABSTRACT: Vav1 regulates Rac activation as a hematopoietic-specific Rho/Rac-family guanine nucleotide exchange factor. Rac is a subfamily of Rho GTPases that regulates the bone-resorbing capacity of osteoclasts (OCs). In this study, we show that hematopoietic-specific Rac2 and Vav1 play opposing roles by enhancing or attenuating OC differentiation, respectively. This was demonstrated by higher and lower bone density in the femurs from Rac2-deficient (Rac2^-/-) and Vav1-deficient (Vav1^-/-) mice, respectively, compared to the wild-type (WT) mice. Accordingly, Rac2^-/- cells displayed low numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (41%) compared to WT cells, whereas, Vav1^-/- cells showed high TRAP-positive cell numbers (

SUBMITTER: Kang IS 

PROVIDER: S-EPMC7184755 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature