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Osteoclast formation is strongly reduced both in vivo and in vitro in the absence of CD47/SIRP{alpha}-interaction

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [3];  [2];  [4];  [2];  [4]
  1. Department of Odontology, Section for Oral Cell Biology, Umeaa University (Sweden) and Neurobiology Program, Garvan Institute of Medical Research, Darlinghurst, NSW (Australia)
  2. Department of Odontology, Section for Oral Cell Biology, Umeaa University (Sweden)
  3. Bone and Mineral Program, Garvan Institute of Medical Research, Darlinghurst, NSW (Australia)
  4. Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeaa University (Sweden)
Physical interaction between the cell surface receptors CD47 and signal regulatory protein alpha (SIRP{alpha}) was reported to regulate cell migration, phagocytosis, cytokine production, and macrophage fusion. However, it is unclear if the CD47/SIRP{alpha}-interaction can also regulate macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-{kappa}B ligand (RANKL)-stimulated formation of osteoclasts. Here, we show that functional blocking antibodies to either CD47 or SIRP{alpha} strongly reduced formation of multinucleated tartrate-resistant acid phosphatase (TRAP){sup +} osteoclasts in cultures of murine hematopoietic cells, stimulated in vitro by M-CSF and RANKL. In addition, the numbers of osteoclasts formed in M-CSF/RANKL-stimulated bone marrow macrophage cultures from CD47 {sup -/-} mice were strongly reduced, and bones of CD47 {sup -/-} mice exhibited significantly reduced osteoclast numbers, as compared with wild-type controls. We conclude that the CD47/SIRP{alpha} interaction is important for M-CSF/RANKL-stimulated osteoclast formation both in vivo and in vitro, and that absence of CD47 results in decreased numbers of osteoclasts in CD47 {sup -/-} mice.
OSTI ID:
20857955
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 352; ISSN BBRCA9; ISSN 0006-291X
Country of Publication:
United States
Language:
English

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