Protease capable of degrading osteoprotegerin in the bone microenvironment.. Mus musculus strain:ICR

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.