Expression profiles of receptor activator of nuclear factor kappa B ligand, receptor activator of nuclear factor kappa B, and osteoprotegerin messenger RNA in aged and ovariectomized rat bones

The receptor activator of nuclear factor-kappaB ligand (RANKL; also known a s tumor necrosis factor-related activation-induced cytokine [TRANCE], osteo protegerin ligand [OPGL], and osteoclast differentiation factor [ODF]) is a transmembrane ligand expressed in osteoblasts and bone marrow stromal cell s. It binds to RANK, which is expressed in osteoclast progenitor cells, and induces osteoclastogenesis. OPG, a decoy receptor for RANKL, also binds to RANKL, and competitive binding of RANKL with RANK or OPG is thought to reg ulate bone metabolism. To investigate roles of the RANKL/RANK/OPG system in pathophysiological conditions, the expression of RANKL, RANK, and OPG mess enger RNA (mRNA) was analyzed in bones of aged and ovariectomized rats by m eans of in situ hybridization. In the control 8-week-old male and sham-oper ated female rat bones, the expression of RANKL mRNA was detected in hypertr ophic chondrocytes of the growth plate and some periosteal and endosteal me senchymal cells. The expression of RANK mRNA was detected in osteoclast-lik e cells and mononuclear cells in contact with the cortical and trabecular b ones. The expression of OPG mRNA was detected in proliferating chondrocytes and osteocytes. In the 2.5-year-old rat bones, the expression of RANKL, RA NK, and OPG mRNA tended to decrease except for the endosteal region. In the ovariectornized rat bones, the expression of RANKL, RANK, and OPG mRNA inc reased, and high expression of OPG mRNA was induced in resting chondrocytes and osteocytes. These results suggest that estrogen deficiency stimulates the RANKL/RANK/OPG system and induces OPG in cells that have been thought t o be less important for bone metabolism.