Smad1 plays an essential role in bone development and postnatal bone formation

Objectives: To determine the role of Smad1 in bone development and postnatal bone formation.

Methods: Col2a1-Cre transgenic mice were bred with Smad1(fx/fx) mice to produce chondrocyte-specific Smad1 conditional knockout (cKO) mice. Embryonic skeletal preparation and staining were performed, alkaline phosphatase activity (ALP) and relative gene expression were examined in isolated primary cells. Smad1(fx/fx) mice were also bred with Col1a1-Cre transgenic mice to produce osteoblast-specific Smad1 cKO mice. Postnatal bone formation was assessed by micro-computed tomography (μCT) and histological analyses in 2-month-old mice. Mineralized bone nodule formation assay, 5-bromo-2'-deoxy-uridine (BrdU) labeling and gene expression analysis were performed.

Results: Mice with chondrocyte- and osteoblast-specific deletion of the Smad1 gene are viable and fertile. Calvarial bone development was delayed in chondrocyte-specific Smad1 cKO mice. In osteoblast-specific Smad1 cKO mice, BMP signaling was partially inhibited and mice developed an osteopenic phenotype. Osteoblast proliferation and differentiation were impaired in osteoblast-specific Smad1 cKO mice.

Conclusions: Smad1 plays an essential role in bone development and postnatal bone formation.