Activation of hedgehog signaling during fracture repair enhances osteoblastic-dependent matrix formation

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Gurpreet S BahtBenjamin A Alman

Abstract

Fracture repair is a well orchestrated process involving various cell types and signaling molecules. The hedgehog signaling pathway is activated in chondrocytes during fracture repair and is known to regulate chondrogenesis however, its role in osteoblasts during injury is yet unknown. In this study we observed tibial fracture repair in mice in which hedgehog signaling was modulated through genetic alterations of the pathway activator, smoothened. Levels of the hedgehog target genes Gli1 and Ptch1 in wildtype mice were upregulated in fracture calluses throughout the repair process. Forced activation of the hedgehog pathway in ubiquitous fashion resulted in increased matrix deposition in the fracture callus. Interestingly, inhibition in chondrocytes did not alter the fracture repair phenotype, while activation of hedgehog in osteoblasts was a requirement for normal fracture repair. In vitro, transcript levels of Gli1 and Ptch1 were elevated during osteoblastogenesis. Activation of hedgehog signaling positively affected osteoblastic differentiation and mineralization as detected using alkaline phosphatase and Von Kossa staining and Alp and Col1 expression. Here we show that the hedgehog signaling pathway plays a critical role in ...Continue Reading

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Citations

Oct 28, 2014·Journal of Orthopaedic Surgery and Research·Shasha ZouHongliang Hu
Jul 30, 2015·Calcified Tissue International·Adeline H NgMarc D Grynpas
Jun 17, 2015·Nature Reviews. Rheumatology·Benjamin A Alman
Aug 24, 2016·Clinical Oral Implants Research·Reinhard GruberHendrik Terheyden
Oct 4, 2016·Biochemical and Biophysical Research Communications·Miki KashiwagiShinsuke Ohba
Apr 18, 2018·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jennifer A McKenzieMichael J Gardner
May 20, 2015·Nature Communications·Gurpreet S BahtBenjamin A Alman
Nov 22, 2016·BoneKEy Reports·Sandeep Paul, J Gage Crump
Apr 16, 2019·ELife·Stephanie T KuwaharaFrancesca V Mariani
Aug 21, 2019·International Journal of Molecular Sciences·Wen-Ting LvChun-Jie Wang
Jun 5, 2017·Molecular and Cellular Biochemistry·Celio J da Costa FernandesWillian F Zambuzzi
Jun 4, 2020·JAAD Case Reports·Valeria CiciarelliMaria Concetta Fargnoli
Jul 31, 2021·Nature Communications·Jun SunMatthew B Greenblatt

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