Regulating Skeletal Progenitor Cells at the Interface Between Tendon and Bone

The surfaces of bones are adorned with projections that mark their integration into the musculoskeletal system. These structures, known as bone eminences, take on diverse shapes and sizes to form anchoring points for tendons and ligaments. Bone eminences represent the mineralized side of the tendon‐bone attachment unit, which is composed of a transitional connective tissue, graded from tendinous to osseous. As such, the eminence plays a critical role transmitting forces generated by muscle contraction and dissipating stress concentrations across the hard‐soft tissue interface. During development, the tendon‐bone attachment unit descends from a unique pool of Scx + /Sox9 + progenitors that form secondary to those of the primary cartilage anlage and later become segregated into Scx + tenocytes or Sox9 + chondrocytes of the eminence (Bltiz et al., 2009, 2013; Sugimoto et al., 2013). While many open questions remain about the molecular regulators that demarcate this boundary across the Scx + /Sox9 + progenitor field, chick embryo studies suggest a role for Fibroblast Growth Factor (FGF) signaling (Brent et al., 2003, 2004, 2005). We have uncovered evidence that Fgfr2 regulates cell fate choice during development of tendon‐bone attachment units in the craniofacial complex of mice. We have found that loss of Fgfr2 increases the eminence superstructure by promoting chondrogenic over tenocytic cell fate in the attachment unit progenitors. These findings contribute to the understanding of tendon‐bone attachment unit development and reveal a possible mechanism to explain the constellation of clinical abnormalities of the tendon‐bone interface that are found in the skeletal birth defects caused by gain and loss of FGFR2 function. Support or Funding Information NIH, NIDCR #1R01DE025222 to A.E.M. March of Dimes, Gene Discovery and Translational Research Grant #6‐FY15‐233 to A.E.M. NIH, NIDCR #T90DE021982 to R.R.