Protease capable of degrading osteoprotegerin in the bone microenvironment.

Osteoclasts are multinucleated cells that are responsible for bone resorption. The differentiation of osteoclasts from bone marrow macrophages (BMM) is induced by receptor activator of NF-kB ligand (RANKL). Osteoprotegerin (OPG), a decoy receptor of RANKL, inhibits osteoclastogenesis by blocking RANKL signaling. In this study, we investigated the degradation of OPG in vitro. We found that osteoclasts, but not BMM, secreted OPG-degrading enzymes. Using mass spectrometry and an RNA-sequencing analysis, we identified candidate protase as an OPG-degrading enzyme. Our results suggest that osteoclasts potentially prepare a microenvironment that is suitable for osteoclastogenesis. This enzyme may be a novel target for drug discovery for bone diseases including osteoporosis.