Teriparatide (1-34 human PTH) regulation of osterix during fracture repair
Article first published online: 20 MAY 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 105, Issue 1, pages 219–226, 1 September 2008
How to Cite
Kaback, L. A., Soung, D. Y., Naik, A., Geneau, G., Schwarz, E. M., Rosier, R. N., O'Keefe, R. J. and Drissi, H. (2008), Teriparatide (1-34 human PTH) regulation of osterix during fracture repair. J. Cell. Biochem., 105: 219–226. doi: 10.1002/jcb.21816
- Issue published online: 21 AUG 2008
- Article first published online: 20 MAY 2008
- Manuscript Accepted: 11 APR 2008
- Manuscript Received: 17 DEC 2007
- National Institutes of Health (NIH) RO1. Grant Number: AR052674-01
- NIH CORT P50. Grant Number: AR05404
Based on remarkable success of PTH as an anabolic drug for osteoporosis, case reports of off-label use of teriparatide (1-34 PTH) in patients with complicated fractures and non-unions are emerging. We investigated the mechanisms underlying PTH accelerated fracture repair. Bone marrow cells from 7 days 40 µg/kg of teriparatide treated or saline control mice were cultured and Osx and osteoblast phenotypic gene expression assessed by real-time RT-PCR in these cells. Fractured animals injected daily with either saline or 40 µg/kg of teriparatide for up to 21 days were X-rayed and histological assessment performed, as well as immunohistochemical analyses of the Osx expression in the fracture callus. Osx, Runx2 and osteoblast or chondrocyte phenotypic gene expression was also assessed in fracture calluses. Our data shows that Osx and Runx2 are up-regulated in marrow-derived MSCs isolated from mice systemically treated with teriparatide. Furthermore, these MSCs undergo accelerated osteoblast maturation compared to saline injected controls. Systemic teriparatide treatments also accelerated fracture healing in these mice concomitantly with increased Osx expression in the PTH treated fracture calluses compared to controls. Collectively, these data suggest a mechanism for teriparatide mediated fracture healing possibly via Osx induction in MSCs. J. Cell. Biochem. 105: 219–226, 2008. © 2008 Wiley-Liss, Inc.