Regulation of osteoblast differentiation by Pasteurella multocida toxin (PMT): a role for Rho GTPase in bone formation.

摘要: The role of the Rho-Rho kinase signaling pathway on osteoblast differentiation was investigated using primary mouse calvarial cells. bacterial toxin PMT inhibited, whereas Rho-ROK inhibitors stimulated, and bone nodule formation. These effects correlated with altered BMP-2 −4 expression. data show importance in formation. Introduction: signal transduction pathways controlling are not well understood. In this study, we used Pasteurella multocida (PMT), a unique that activates small GTPase Rho, specific Rho to investigate formation vitro. Materials Methods: Primary cultures were recombinant (ROK) Osteoblast gene expression analyzed Northern blot RT-PCR, actin rearrangements visualized after phalloidin staining confocal microscopy. Results: stimulated proliferation cells markedly inhibited precursors nodules concomitant inhibition osteoblastic marker There no apparent causal relationship between stimulation differentiation. caused cytoskeletal because activation completely reversed by inhibitor C3 transferase partly effector, ROK. Interestingly, ROK alone potently differentiation, expression, Finally, morphogenetic protein (BMP)-2 mRNA providing possible mechanism for their formation. Conclusions: results inhibits through involving is an important negative regulator Conversely, stimulate may be potentially useful as anabolic agents bone.