Deletion of Fibroblast growth factor 9 globally and in skeletal muscle results in enlarged tuberosities at sites of deltoid tendon attachments

February 28, 2021

Connor C. Leek (1,2), Jaclyn M. Soulas (1,3), Iman Bhattacharya (1,4), Elahe Ganji (1,2), Ryan C. Locke (1), Megan C. Smith (1,5,6), Jaysheel D. Bhavsar (4), Shawn W. Polson (1,4), David M. Ornitz (7), Megan L. Killian (1,2)

BioRxiv 23 February 2021. DOI: 10.1101/2021.02.23.432498


Skeleton; Enthesis; Bone shape; Muscle


The growth of most bony tuberosities, like the deltoid tuberosity (DT), rely on the transmission of muscle forces at the tendon-bone attachment during skeletal growth. Tuberosities distribute muscle forces and provide mechanical leverage at attachment sites for joint stability and mobility. The genetic factors that regulate tuberosity growth remain largely unknown. In mouse embryos with global deletion of fibroblast growth factor 9 (Fgf9), the DT size is notably enlarged. In this study, we explored the tissue-specific regulation of DT size using both global and targeted deletion of Fgf9. We showed that cell hypertrophy and mineralization dynamics of the DT, as well as transcriptional signatures from skeletal muscle but not bone, were influenced by the global loss of Fgf9. Loss of Fgf9 during embryonic growth led to increased chondrocyte hypertrophy and reduced cell proliferation at the DT attachment site. This endured hypertrophy and limited proliferation may explain the abnormal mineralization patterns and locally dysregulated expression of markers of endochondral development in Fgf9null attachments. We then showed that targeted deletion of Fgf9 in skeletal muscle leads to postnatal enlargement of the DT. Taken together, we discovered that Fgf9 may play an influential role in muscle-bone crosstalk during embryonic and postnatal development.

How Our Software Was Used

Dragonfly was used to reconstruct and analyze micro-ct data.

Author Affiliation

(1) College of Engineering, University of Delaware, Newark, Delaware, 19716, USA
(2) Department of Orthopaedic Surgery, Michigan Medicine, Ann Arbor, Michigan, 48109, USA
(3) College of Agriculture and Natural Resources, University of Delaware, Newark, Delaware, 19716, USA
(4) Center for Bioinformatics and Computational Biology, University of Delaware, Newark, Delaware, 19713, USA
(5) Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
(6) Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA
(7) Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, 63110, USA