Teriparatide (1-34 human PTH) regulation of osterix during fracture repair.
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 microg/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 microg/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.
Kaback
Lee A
LA
The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA.
Soung
Do Y
do Y
Naik
Amish
A
Geneau
Graziello
G
Schwarz
Edward M
EM
Rosier
Randy N
RN
O'Keefe
Regis J
RJ
Drissi
Hicham
H
D000818:Animals; D015415:Biomarkers; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017102:Fracture Healing / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D000076182:Sp7 Transcription Factor; D013234:Stem Cells / Q000378:metabolism; D019379:Teriparatide / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D019379:Teriparatide