Identification of genes differentially expressed in osteoclast-like cells.

Homeostasis of the skeletal system is maintained by a balance between bone formation and resorption. The receptor activator of NF-kappaB ligand (RANKL) induces the differentiation of bone-resorbing cells, osteoclasts. To identify genes regulated during osteoclast differentiation, we constructed a subtraction cDNA library using a mouse RAW264 macrophage cell line that differentiates into osteoclast-like multinucleated cells after treatment with RANKL. Northern blot analysis showed that RANKL treatment upregulated expression of 17 genes. Among these were the genes for five H(+)-ATPase subunits, two chemokines, and the osteoclast marker cathepsin K. In addition, a mouse homolog of human dendritic cell (DC)-specific transmembrane protein (DCSTAMP), whose function in osteoclastogenesis was recently revealed, was also included in the induced genes. Characterization of these inducible genes will provide an insight into the biology of osteoclasts and the mechanism of bone-related diseases.