XXXX signaling in osteoclasts is negatively regulated by the BMP antagonist, twisted gastrulation.

@entity19 @entity5271 @entity2331 @entity8385 @entity65349
Bone morphogenetic proteins (BMPs) have been shown to regulate both osteoblasts and osteoclasts. We previously reported that @entity8385 could directly enhance @entity5271 -mediated osteoclast differentiation by increasing the size and number of osteoclasts. Similarly, genetic deletion of the BMP antagonist Twisted gastrulation ( @entity65349 ) in @entity19 , resulted in an enhancement of osteoclast formation, activity and @entity2331 . This was accompanied by increased levels of phosphorylated Smad (pSmad) 1/5/8 in @entity65349 (-/-) osteoclasts in vitro. The purpose of this study was to develop an adenoviral vector overexpressing @entity65349 as a means of inhibiting osteoclast activity. We demonstrate that overexpressing @entity65349 in primary osteoclasts decreased the size and number of multinuclear TRAP-positive osteoclasts, expression of osteoclast genes, and resorption ability. Overexpression of @entity65349 did not affect osteoclast proliferation or apoptosis. However, overexpression of @entity65349 decreased the levels of pSmad 1/5/8 in osteoclasts. Addition of exogenous @entity8385 to osteoclasts overexpressing @entity65349 rescued the size and levels of pSmad 1/5/8 compared to cultures infected with a control virus. Finally, @entity65349 overexpression in osteoclasts isolated from the @entity65349 (-/-) @entity19 rescued size of the osteoclasts while further addition of exogenous @entity8385 reversed the effect of @entity65349 overexpression and increased the size of the osteoclasts similar to control virus infected cells. Taken together, we demonstrate that overexpressing @entity65349 in osteoclasts via an adenoviral vector results in inhibition of osteoclastogenesis and may provide a potential therapy for inhibiting osteoclast activity in a localized manner.
