BoneKEy Reports | BoneKEy Watch

Gpr177 is essential for skeletogenesis

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DOI:10.1038/bonekey.2013.32

Genome-wide association studies recently identified Gpr177 (the mouse orthologue of Drosophila Wls) as a susceptibility locus for bone mineral density and osteoporosis. Gpr177 encodes a protein that modulates Wnt trafficking and is therefore thought to have a potential role in bone development.

In this study, Maruyama et al. generated four transgenic mouse strains deficient in Gpr177 in mesenchymal cells, osteoprogenitor cells, osteoblasts and chondrocytes. Deletion of Gpr177 in mesenchymal cells led to abnormal development of the craniofacial skeleton, mice that lacked the gene in osteoprogenitor cells showed delayed mineralization in calvaria, but mice with a Gpr177 knock-out specific for osteoblasts showed no skeletal deformities. Mice that could not express the gene in chondrocytes showed abnormal formation of the axial and appendicular bones; the expression of Gpr177 was required for endochondral ossification.

Mesenchymal Gpr177 was found to be essential for Wnt production and for activating β-catenin signaling, so was necessary for driving precursor cells to differentiate into osteoblast cell types. The authors conclude that mesenchymal cells are the primary source of Wnt, which promotes β-catenin signaling in other mesenchymal cells and in osteoblast precursors.

Editor’s comment: This study not only reveals the requirement for Gpr177 in osteogenesis and chondrogenesis, but also identifies its essential function in modulating the interplay of Wnt signals across distinct cell types in skeletal development.

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