Osteoprotegerin deficiency attenuates strontium‐mediated inhibition of osteoclastogenesis and bone resorption |
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Authors: | Songlin Peng X Sherry Liu Guangqian Zhou Zhaoyang Li Keith DK Luk X Edward Guo W William Lu |
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Affiliation: | 1. Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong;2. Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, USA;3. Division of Endocrinology, Department of Medicine, Columbia University, New York, NY, USA |
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Abstract: | Strontium (Sr) exerts an anabolic and antiresorptive effect on bone, but the mechanism remains unknown. Osteoprotegerin (OPG) expressed by osteoblasts plays an important role in regulating bone homeostasis by inhibiting osteoclastogenesis and bone resorption. This study aims at evaluating the role of OPG in Sr‐mediated inhibition of osteoclastogenesis and bone resorption. Six‐week‐old Opg knockout (KO) male mice and their wild‐type (WT) littermates were treated orally with vehicle (Veh) or Sr compound (4 mmol/kg) daily for 8 weeks. Bone mass and microstructure in the lumbar spine (L4) and proximal tibia were analyzed with micro–computed tomography (µCT). Bone remodeling was evaluated with serum biochemical analysis and static and dynamic bone histomorphometry. Osteoclast differentiation potential and gene expression were analyzed in bone marrow cells. The findings demonstrate that Sr compound treatment results in greater bone volume and trabecular number than Veh treatment in WT mice. The anabolic response of trabecular bone to Sr treatment is attenuated in KO mice. Although Sr treatment significantly decreases in vitro osteoclastogenesis and bone resorption in WT mice, these effects are attenuated in KO mice. Furthermore, Sr treatment profoundly increases Opg gene expression in the tibias and OPG protein levels in the sera of WT mice. This study concludes that the inhibition of osteoclastogenesis and bone resorption is possibly associated with OPG upregulation by Sr treatment. © 2011 American Society for Bone and Mineral Research. |
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Keywords: | Osteoprotegerin Strontium Bone Formation Bone Resorption Osteoporosis |
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