Recombinant receptor activator of nuclear factor κB exhibits more marked inhibitory effects on osteoclasts compared with recombinant osteoprotegerin in vitro and in vivo.
The aim of the present study was to compare the osteoclast-inhibiting ability of recombinant osteoprotegerin (OPG) protein (rhOPG-Fc) and recombinant receptor activator of nuclear factor κB (rhRANK) in vitro and in vivo. Osteoclasts were cultured with either rhOPG-Fc or rhRANK for 9 days. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and resorption pits in bone slices were then counted. In the in vivo investigation, female mice were bilaterally ovariectomized (OVX) and intraperitoneally injected with 3 mg/kg rhOPG-Fc or rhRANK for 12 weeks, respectively. Bone metabolism, bone mineral density and microstructure changes were then evaluated. The number of TRAP-positive cells and bone resorption pits decreased significantly following culture with either rhOPG-Fc or rhRANK, and this was more marked following culture with rhRANK compared with rhOPG-Fc. The levels of calcium and alkaline phosphatase in the serum were similar pre-OVX and after 12 weeks of treatment, while the levels of phosphorus in the serum were higher following treatment with rhRANK compared with rhOPG. The bone mineral density (BMD) of the whole body, femoral neck and L4 lumbar vertebral body in the mice treated with either rhOPG-Fc or rhRANK increased markedly. In addition, the mice treated with rhRANK exhibited significantly higher BMD in the femoral neck and lumbar vertebral body compared with those treated with rhOPG-Fc. Microcomputed tomography analysis demonstrated that the mice treated with rhRANK exhibited an increased bone volume and structure model index, and decreased trabecular spacing compared with those treated with rhOPG-Fc. rhRANK increased the inhibition of osteoclast differentiation and bone resorption, and rescued OVX-induced osteoporosis more effectively compared with rhOPG-Fc.
Department of Orthopedics, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
Qi
Q
Xiong
Department of Obstetrics and Gynecology, The Second Artillery General Hospital of Chinese PLA, Beijing 100088, P.R. China.
Lingli
L
Xin
Department of Orthopedics, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
Licheng
L
Zhang
Department of Orthopedics, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
Peifu
P
Tang
Department of Orthopedics, General Hospital of Chinese PLA, Beijing 100853, P.R. China.
Lihai
L
Zhang
D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053244:Osteoprotegerin / Q000008:administration & dosage* / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000008:administration & dosage* / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics
D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; D011994:Recombinant Proteins; C505686:TNFRSF11A protein, human