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The MSC marker CD248 (Endosialin) is a negative regulator of bone formation


Naylor, Amy J; Azzam, Eman; Smith, Stuart; Croft, Adam; Poyser, Callum; Duffield, Jeremy S; Huso, David L; Gay, Steffen; Ospelt, Caroline; Cooper, Mark S; Isacke, Clare; Goodyear, Simon; Rogers, Michael J; Buckley, Christopher D (2012). The MSC marker CD248 (Endosialin) is a negative regulator of bone formation. Arthritis and Rheumatism, 64(10):3334-3343.

Abstract

OBJECTIVE: CD248 (TEM1/Endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. The CD248 knockout (CD248(-/-) ) mouse has reduced inflammatory arthritis. The aim of this study was to investigate the functional effect of genetic deletion of CD248 on bone mass. METHODS: Western blotting, PCR and immunofluorescence were used to investigate CD248 expression. MicroCT and 3-point bending of tibiae from 10 week old wildtype or CD248(-/-) were used to measure bone parameters and mechanical properties. Primary osteoblasts were cultured in media containing 10 mM β-glycerophosphate and 50 μg/ml ascorbic acid to induce mineralisation and treated with PDGF-BB. Mineral apposition rate in vivo was calculated by labelling newly formed bone with calcein. RESULTS: Expression of CD248 was seen in human and mouse osteoblasts but not osteoclasts. CD248(-/-) tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT. CD248(-/-) primary osteoblasts had increased mineralisation in vitro and produced increased bone over 7 days in vivo and failed to decrease mineralisation or increase proliferation in response to PDGF-BB stimulation due to a defect in PDGF signal transduction. CONCLUSION: There is an unmet clinical need to address RA-associated bone loss. Genetic deletion of CD248 in the mouse 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 as well as the previously reported effect of reducing inflammation.

Abstract

OBJECTIVE: CD248 (TEM1/Endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. The CD248 knockout (CD248(-/-) ) mouse has reduced inflammatory arthritis. The aim of this study was to investigate the functional effect of genetic deletion of CD248 on bone mass. METHODS: Western blotting, PCR and immunofluorescence were used to investigate CD248 expression. MicroCT and 3-point bending of tibiae from 10 week old wildtype or CD248(-/-) were used to measure bone parameters and mechanical properties. Primary osteoblasts were cultured in media containing 10 mM β-glycerophosphate and 50 μg/ml ascorbic acid to induce mineralisation and treated with PDGF-BB. Mineral apposition rate in vivo was calculated by labelling newly formed bone with calcein. RESULTS: Expression of CD248 was seen in human and mouse osteoblasts but not osteoclasts. CD248(-/-) tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT. CD248(-/-) primary osteoblasts had increased mineralisation in vitro and produced increased bone over 7 days in vivo and failed to decrease mineralisation or increase proliferation in response to PDGF-BB stimulation due to a defect in PDGF signal transduction. CONCLUSION: There is an unmet clinical need to address RA-associated bone loss. Genetic deletion of CD248 in the mouse 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 as well as the previously reported effect of reducing inflammation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:12 Jul 2012 06:07
Last Modified:05 Apr 2016 15:52
Publisher:Wiley-Blackwell
ISSN:0004-3591
Publisher DOI:https://doi.org/10.1002/art.34556
PubMed ID:22674221

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