Targeted deletion of Fgf9 in tendon disrupts mineralization of the developing enthesis

FASEB J. 2023 Mar;37(3):e22777. doi: 10.1096/fj.202201614R.

Abstract

The enthesis is a transitional tissue between tendon and bone that matures postnatally. The development and maturation of the enthesis involve cellular processes likened to an arrested growth plate. In this study, we explored the role of fibroblast growth factor 9 (Fgf9), a known regulator of chondrogenesis and vascularization during bone development, on the structure and function of the postnatal enthesis. First, we confirmed spatial expression of Fgf9 in the tendon and enthesis using in situ hybridization. We then used Cre-lox recombinase to conditionally knockout Fgf9 in mouse tendon and enthesis (Scx-Cre) and characterized enthesis morphology as well as mechanical properties in Fgf9ScxCre and wild-type (WT) entheses. Fgf9ScxCre mice had smaller calcaneal and humeral apophyses, thinner cortical bone at the attachment, increased cellularity, and reduced failure load in mature entheses compared to WT littermates. During postnatal development, we found reduced chondrocyte hypertrophy and disrupted type X collagen (Col X) in Fgf9ScxCre entheses. These findings support that tendon-derived Fgf9 is important for functional development of the enthesis, including its postnatal mineralization. Our findings suggest the potential role of FGF signaling during enthesis development.

Keywords: attachment; enthesis; fibroblast growth factor; musculoskeletal; postnatal; tendon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Development / genetics
  • Bone and Bones
  • Chondrogenesis
  • Fibroblast Growth Factor 9* / genetics
  • Fibroblast Growth Factor 9* / metabolism
  • Mice
  • Tendons* / metabolism

Substances

  • Fibroblast Growth Factor 9
  • Fgf9 protein, mouse