T. Gaur and J.J. Wixted contributed equally to this study.
Article first published online: 19 MAR 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 220, Issue 1, pages 174–181, July 2009
How to Cite
Gaur, T., Wixted, J. J., Hussain, S., O'Connell, S. L., Morgan, E. F., Ayers, D. C., Komm, B. S., Bodine, P. V., Stein, G. S. and Lian, J. B. (2009), Secreted frizzled related protein 1 is a target to improve fracture healing. J. Cell. Physiol., 220: 174–181. doi: 10.1002/jcp.21747
The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
- Issue published online: 23 APR 2009
- Article first published online: 19 MAR 2009
- Manuscript Accepted: 30 JAN 2009
- Manuscript Received: 27 JAN 2009
- NIH. Grant Numbers: R01 AR039588, R37 DE012528, P30 DK32520
Genetic studies have identified a high bone mass of phenotype in both human and mouse when canonical Wnt signaling is increased. Secreted frizzled related protein 1 (sFRP1) is one of several Wnt antagonists and among the loss-of-function mouse models in which 32-week-old mice exhibit a high bone mass phenotype. Here we show that impact fracture healing is enhanced in this mouse model of increased Wnt signaling at a physiologic level in young (8 weeks) sFRP1−/− mice which do not yet exhibit significant increases in BMD. In vivo deletion of sFRP1 function improves fracture repair by promoting early bone union without adverse effects on the quality of bone tissue reflected by increased mechanical strength. We observe a dramatic reduction of the cartilage callous, increased intramembranous bone formation with bone bridging by 14 days, and early bone remodeling during the 28-day fracture repair process in the sFRP1−/− mice. Our molecular analyses of gene markers indicate that the effect of sFRP1 loss-of-function during fracture repair is to accelerate bone healing after formation of the initial hematoma by directing mesenchymal stem cells into the osteoblast lineage via the canonical pathway. Further evidence to support this conclusion is the observation of maximal sFRP1 levels in the cartilaginous callus of a WT mouse. Hence sFRP1−/− mouse progenitor cells are shifted directly into the osteoblast lineage. Thus, developing an antagonist to specifically inhibit sFRP1 represents a safe target for stimulating fracture repair and bone formation in metabolic bone disorders, osteoporosis and aging. J. Cell. Physiol. 220: 174–181, 2009. © 2009 Wiley-Liss, Inc.