Abstract
Integrin-associated protein (IAP/CD47) has been implicated in macrophage-macrophage fusion. To understand the actions of CD47 on skeletal remodeling, we compared Cd47 -/- mice with Cd47 +/+ controls. Cd47 -/- mice weighed less and had decreased areal bone mineral density compared with controls. Cd47 -/- femurs were shorter in length with thinner cortices and exhibited lower trabecular bone volume owing to decreased trabecular number and thickness. Histomorphometry revealed reduced bone-formation and mineral apposition rates, accompanied by decreased osteoblast numbers. No differences in osteoclast number were observed despite a nonsignificant but 40% decrease in eroded surface/bone surface in Cd47 -/- mice. In vitro, the number of functional osteoclasts formed by differentiating Cd47 -/- bone marrow cells was significantly decreased compared with wild-type cultures and was associated with a decrease in bone-resorption capacity. Furthermore, by disrupting the CD47-SHPS-1 association, we found that osteoclastogenesis was markedly impaired. Assays for markers of osteoclast maturation suggested that the defect was at the point of fusion and not differentiation and was associated with a lack of SHPS-1 phosphorylation, SHP-1 phosphatase recruitment, and subsequent dephosphorylation of non-muscle cell myosin IIA. We also demonstrated a significant decrease in osteoblastogenesis in bone marrow stromal cells derived from Cd47 -/- mice. Our finding of cell-autonomous defects in Cd47 -/- osteoblast and osteoclast differentiation coupled with the pronounced skeletal phenotype of Cd47 -/- mice support the conclusion that CD47 plays an important role in regulating skeletal acquisition and maintenance through its actions on both bone formation and bone resorption.
Original language | English (US) |
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Pages (from-to) | 2068-2081 |
Number of pages | 14 |
Journal | Journal of Bone and Mineral Research |
Volume | 26 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2011 |
Externally published | Yes |
Keywords
- BONE
- BONE RESORPTION
- NON-MUSCLE CELL MYOSIN IIA
- OSTEOBLAST
- OSTEOCLAST
- SHP-1
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine