Regulation of osteoprotegerin localization and expression in bone remodeling

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Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor family, works as a decoy by binding to receptor activator of nuclear factor (NF)-kB ligand (RANKL) and thus inhibits osteoclastogenesis by interrupting RANKL-mediated signaling. We investigated the localization of OPG in rat tibia using a specific peptide antibody and its expression by in situ hybridization in order to clarify the role of OPG in bone remodeling. Western blotting showed that the antibody reacted with a 90 kD band in lysate from rat tibiae. Immunohistochemical observation revealed that OPG reactivity was mainly seen on bone surfaces under osteoclasts. In bone matrices, OPG was also localized on cartilage/bone interfaces and cement lines. However, labeling was hardly detected in the region of contact between osteoclasts and stromal cells. Some osteoblasts and osteocytes showed weak labeling. These findings suggest that OPG derived from osteoblast-lineage cells and/or serum may be concentrated on resorbed bone surfaces, and subsequently on cement lines. OPG may play an important role in the prevention of excess bone resorption by inhibiting differentiation and activity of osteoclasts in bone remodeling. Since OPG has high affinity for heparin, we also compared the localization of proteoglycans, such as hyaluronate, heparan sulfate, keratan sulfate and chondroitin sulfate proteoglycans. However, their patterns are different from OPG. The mechanism of OPG localization in bone matrix should be addressed in future research.