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Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin
1Research Institute of Life Science, Snow Brand Milk Products, Co., Ltd., Tochigi, Japan.
Abstract:
Osteoclasts are multinucleated cells that resorb bone. Osteoclastogenesis inhibitory factor (OCIF), also called osteoprotegerin (OPG), acts as a naturally occurring decoy receptor for osteoclast differentiation factor, which mediates an essential signal to osteoclast progenitors for their differentiation into osteoclasts. Here we show that the OCIF/OPG knockout mice exhibited severe osteoporosis due to enhanced osteoclastogenesis when they grew to be adults. These mice were viable and fertile. They exhibited marked bone loss accompanied by destruction of growth plate and lack of trabecular bone in their femurs. The strength of their bones dramatically decreased. These results demonstrate that OCIF/OPG is a key factor acting as a negative regulator against osteoclastogenesis. The OCIF/OPG knockout mice provide the first animal model for osteoporosis without other obvious abnormalities.
Insights
Osteoprotegerin (OPG) inhibits bone-resorbing osteoclast formation. OPG knockout mice develop severe osteoporosis, confirming OPG
Area of Science:
- Bone Biology and Skeletal Diseases
- Cellular and Molecular Medicine
Background:
- Osteoclasts are critical for bone resorption.
- Osteoclastogenesis inhibitory factor (OCIF), also known as osteoprotegerin (OPG), functions as a decoy receptor.
- OCIF/OPG regulates osteoclast differentiation by inhibiting the osteoclast differentiation factor signaling pathway.
Purpose of the Study:
- To investigate the role of OCIF/OPG in regulating osteoclastogenesis and bone metabolism.
- To characterize the phenotype of OCIF/OPG knockout mice.
Main Methods:
- Generation and analysis of OCIF/OPG knockout mice.
- Assessment of bone loss, osteoclastogenesis, and bone structure in adult knockout mice.
- Evaluation of femur bone properties and growth plate integrity.
Main Results:
- OCIF/OPG knockout mice exhibited severe osteoporosis with significant bone loss.
- Enhanced osteoclastogenesis was observed in the absence of OCIF/OPG.
- Knockout mice showed growth plate destruction, reduced trabecular bone, and decreased bone strength.
Conclusions:
- OCIF/OPG is a crucial negative regulator of osteoclastogenesis.
- The absence of OCIF/OPG leads to severe bone loss and osteoporosis.
- OCIF/OPG knockout mice represent a valuable model for studying osteoporosis.