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CD47 regulates bone mass and tumor metastasis to bone
Ozge Uluçkan1, Stephanie N Becker, Hongju Deng
1Division of Oncology, Department of Medicine and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cancer Research
|March 12, 2009
Summary
CD47 deficiency increases bone mass and reduces bone metastasis by impairing osteoclast function, partly through nitric oxide regulation. This highlights CD47 as a therapeutic target for bone diseases and cancer metastasis.
Area of Science:
- Immunology
- Skeletal Biology
- Oncology
Background:
- CD47 (integrin-associated protein) is crucial for innate immunity and beta3 integrin activation.
- Beta3 integrin-deficient mice exhibit impaired platelet and osteoclast function, with protection from bone metastasis.
- The specific roles of CD47 in skeletal homeostasis and bone metastasis were previously undescribed.
Purpose of the Study:
- To investigate the function of CD47 in skeletal homeostasis.
- To determine the role of CD47 in bone metastasis.
- To elucidate the mechanisms underlying CD47's effects on osteoclastogenesis and bone metastasis.
Main Methods:
- Analysis of bone mass and osteoclast function in CD47(-/-) mice.
- In vitro osteoclast differentiation assays using CD47(-/-) bone marrow macrophages.
- In vivo studies of tumor metastasis to bone in CD47(-/-) and wild-type mice.
- Assessment of nitric oxide (NO) synthase expression and inhibition.
Main Results:
- CD47(-/-) mice displayed increased bone mass and defective osteoclast function in vivo.
- Osteoclast differentiation and function were reduced in CD47(-/-) cells, but could be rescued by high doses of RANKL or NO synthase inhibition.
- Tumor burden and tumor-associated bone destruction were decreased in CD47(-/-) mice during bone metastasis.
- CD47(-/-) mice showed no defect in subcutaneous tumor growth, indicating a specific effect on bone metastasis.
Conclusions:
- CD47 regulates osteoclastogenesis, partly through the modulation of NO production.
- Disruption of CD47 function leads to enhanced bone mass and reduced bone metastasis.
- CD47 represents a potential therapeutic target for increasing bone mass and decreasing metastatic tumor growth in bone.
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