Role of OPG in regulation of bone remodeling

Abstract

Osteoprotegerine (OPG) acts as a decoy receptor for receptor activator of NF-kappaB (RANK) ligand (RANKL) to compete against RANK. OPG-deficient mice exhibit severe osteoporosis with accelerated bone remodeling. In human, several homozygous mutations in OPG gene were found in patients with juvenile Paget's disease. Missense mutations in cysteine residues in ligand binding domain, as well as complete deletion mutation, were associated with a severe phenotype characterized by enhanced bone remodeling and deformity. Serum RANKL level was elevated in OPG-deficient mice and a patient with complete deletion mutation. These results suggest that OPG represses the production of soluble form of RANKL. The elevated RANKL level in serum of OPG-deficient mice was not reduced by treatment with anti-resorbing agent, risedronate, but was upregulated by 1,25 (OH) (2)D(3) administration or ovariectomy.