Involvement of the Mab21l1 gene in calvarial osteogenesis.

The Mab-21 gene family is crucial for animal development. A deficiency in the Mab-21 genes associates with several defects, including skeletal malformation in mice and humans. In this study, we observed that mice lacking Mab21l1 displayed an unclosed fontanelle, suggesting impaired calvarial bone development. Cells isolated from the calvaria of these mice showed a greater osteoblast differentiation potential as evidenced by the abundance of mineralized bone nodules and higher expression levels of osteogenic markers than wild-type cells. Mab21l1-/- osteoblasts also expressed higher levels of adipocyte genes and interferon-regulated genes at early stages of osteogenesis. Rankl/Opg expression levels were also higher in Mab21l1-/- osteoblasts than in wild-type cells. These data suggest that Mab21l1 is involved in either the regulation of mesenchymal cell proliferation and differentiation or the balance between bone formation and resorption. An alteration in these regulatory machineries, therefore, may lead to insufficient bone formation, causing the bone phenotype in Mab21l1-/- mice.