Expression of RANKL/OPG during bone remodeling in vivo

• Published in: Biochemical and biophysical research communications 2011-08, Vol.411 (4), p.690-694
• Main Authors: Tanaka, H., Mine, T., Ogasa, H., Taguchi, T., Liang, C.T.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ABLATION; ALKALINE PHOSPHATASE; Animals; Bone marrow; BONE MARROW CELLS; Bone remodeling; Bone Remodeling - genetics; Bone remodelling; Bone resorption; FEMUR; Femur - metabolism; Gene Expression; Gene Expression Regulation, Developmental; GENES; Genetic Markers; Immunoreactivity; IN VIVO; LIGANDS; Male; MESSENGER-RNA; Osteoblastogenesis; Osteoblasts; Osteoblasts - metabolism; Osteocalcin; Osteoclastogenesis; Osteogenesis; Osteogenesis - genetics; Osteopontin; Osteoprotegerin; Osteoprotegerin (OPG); Osteoprotegerin - genetics; Osteoprotegerin - metabolism; POLYMERASE CHAIN REACTION; procollagen; RANK Ligand - genetics; RANK Ligand - metabolism; RATS; Rats, Wistar; Receptor activator of nuclear factor κB ligand (RANKL); RECEPTORS; TRANCE protein
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.07.001

► This is the first study to determine the relationship between osteogenic differentiation and RANKL/OPG expression during bone remodeling in vivo. ► The OPG expression peak occurred during the bone formation phase, whereas the marked elevation of RANKL expression was observed during the bone resorption phase. ► Histological analysis showed that RANKL/OPG immunoreactivity was predominantly associated with bone marrow cells in the marrow cavity. ► The present study confirmed that RANKL/OPG are key factors linking bone formation to resorption during the bone remodeling process. The interaction between receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation. Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen α1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The expression of bone formation markers was activated in the bone formation phase, followed by the stimulation of RANKL/OPG expression in the bone resorption phase, which confirmed that these molecules are key factors linking bone formation to resorption during bone remodeling.