Osteoblast-Derived FGF9 Regulates Skeletal Homeostasis

Authors

Liping Wang, University of California - San Francisco
Theresa M. Roth, University of California - San Francisco
Marcia J. Abbott, Chapman UniversityFollow
Linh Ho, University of California - San Francisco
Lalita Wattanachanya, University of California - San Francisco
Robert A. Nissenson, University of California - San Francisco

Document Type

Article

Publication Date

2-9-2017

Abstract

FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9^{OB −/−}). Both Fgf9 knockout (Fgf9^{OB −/−}) and the Fgf9 floxed littermates (Fgf9^fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three month old Fgf9^{OB −/−} mice displayed a significant decrease in cancellous bone and bone formation in the distal femur and a significant decrease in cortical thickness at the TFJ. Strikingly, female Fgf9^{OB −/−} mice did not display altered bone mass. Continuous treatment of mouse BMSCs with exogenous FGF9 inhibited mouse BMSC mineralization while acute treatment increased the proliferation of progenitors, an effect requiring the activation of Akt1. Our results suggest that mature OBs are an important source of FGF9, positively regulating skeletal homeostasis in male mice. Osteoblast-derived FGF9 may serve a paracrine role to maintain the osteogenic progenitor cell population through activation of Akt signaling.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Bone. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version will subsequently be published in Bone in 2017. DOI:10.1016/j.bone.2016.12.005

The Creative Commons license below applies only to this version of the article.

Recommended Citation

Wang L, Roth T, Abbott M, Ho L, Wattanachanya L, Nissenson RA. Osteoblast-derived FGF9 regulates skeletal homeostasis. Bone. 2016. doi: 10.1016/j.bone.2016.12.005

Peer Reviewed

1

Copyright

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.