| First Author | Naylor AJ | Year | 2012 |
| Journal | Arthritis Rheum | Volume | 64 |
| Issue | 10 | Pages | 3334-43 |
| PubMed ID | 22674221 | Mgi Jnum | J:327851 |
| Mgi Id | MGI:6870588 | Doi | 10.1002/art.34556 |
| Citation | Naylor AJ, et al. (2012) The mesenchymal stem cell marker CD248 (endosialin) is a negative regulator of bone formation in mice. Arthritis Rheum 64(10):3334-43 |
| abstractText | OBJECTIVE: CD248 (tumor endothelial marker 1/endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. Studies have shown a reduction in inflammatory arthritis in CD248-knockout (CD248(-/-) ) mice. The aim of the present study was to investigate the functional effect of genetic deletion of CD248 on bone mass. METHODS: Western blotting, polymerase chain reaction, and immunofluorescence were used to investigate the expression of CD248 in humans and mice. Micro-computed tomography and the 3-point bending test were used to measure bone parameters and mechanical properties of the tibiae of 10-week-old wild-type (WT) or CD248(-/-) mice. Human and mouse primary osteoblasts were cultured in medium containing 10 mM beta-glycerophosphate and 50 mug/ml ascorbic acid to induce mineralization, and then treated with platelet-derived growth factor BB (PDGF-BB). The mineral apposition rate in vivo was calculated by identifying newly formed bone via calcein labeling. RESULTS: Expression of CD248 was seen in human and mouse osteoblasts, but not osteoclasts. CD248(-/-) mouse tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT mice. Primary osteoblasts from CD248(-/-) mice induced increased mineralization in vitro and produced increased bone over 7 days in vivo. There was no decrease in bone mineralization and no increase in proliferation of osteoblasts in response to stimulation with PDGF-BB, which could be attributed to a defect in PDGF signal transduction in the CD248(-/-) mice. CONCLUSION: There is an unmet clinical need to address rheumatoid arthritis-associated bone loss. Genetic deletion of CD248 in mice results in high bone mass due to increased osteoblast-mediated bone formation, suggesting that targeting CD248 in rheumatoid arthritis may have the effect of increasing bone mass in addition to the previously reported effect of reducing inflammation. |
