Bone morphogenetic proteins (BMPs) activate the canonical Smad1/5/8 and
non-canonical Tak1-MAPK pathways via BMP
receptors I and II to regulate skeletal
development and bone remodeling. Specific ablation of
Bmpr1a
in immature
osteoblasts, osteoblasts, or osteocytes results in an increase in
cancellous
bone mass,
yet opposite results have been reported regarding the underlying mechanisms.
Moreover, the role for BMPRIA-mediated signaling in bone marrow mesenchymal
stromal cells (BM-MSCs) has not been explored. Here, we specifically ablated
Bmpr1a
in BM-MSCs in adult mice to study the function of BMPR1A in bone
remodeling and found that the mutant mice showed an increase in cancellous
and
cortical bone mass, which was accompanied by a decrease in bone formation rate and
a greater decrease in bone resorption. Decreased bone formation was associated with
a defect in BM-MSC osteogenic differentiation whereas decreased bone resorption
was associated with a decrease in RANKL production and osteoclastogenesis.
However, ablation of
Ta k 1
, a critical non-canonical signaling molecule downstream of
BMP receptors, in BM-MSCs at adult stage did not affect bone remodeling. These
results suggest that BMP signaling through BMPRIA controls BM-MSC osteogenic
differentiation/bone formation and RANKL ex
pression/osteoclastogenesis in adult
mice independent of Tak1 signaling.