Department of Biomedical Engineering, University of Delaware, Newark, Delaware, USA.
Institute of Anatomy, University of Zürich, Zürich, Switzerland.
Dev Dyn. 2023 Sep;252(9):1180-1188. doi: 10.1002/dvdy.600. Epub 2023 May 22.
Tendons and ligaments attach to bone are essential for joint mobility and stability in vertebrates. Tendon and ligament attachments (ie, entheses) are found at bony protrusions (ie, eminences), and the shape and size of these protrusions depend on both mechanical forces and cellular cues during growth. Tendon eminences also contribute to mechanical leverage for skeletal muscle. Fibroblast growth factor receptor (FGFR) signaling plays a critical role in bone development, and Fgfr1 and Fgfr2 are highly expressed in the perichondrium and periosteum of bone where entheses can be found.
We used transgenic mice for combinatorial knockout of Fgfr1 and/or Fgfr2 in tendon/attachment progenitors (ScxCre) and measured eminence size and shape. Conditional deletion of both, but not individual, Fgfr1 and Fgfr2 in Scx progenitors led to enlarged eminences in the postnatal skeleton and shortening of long bones. In addition, Fgfr1/Fgfr2 double conditional knockout mice had more variation collagen fibril size in tendon, decreased tibial slope, and increased cell death at ligament attachments. These findings identify a role for FGFR signaling in regulating growth and maintenance of tendon/ligament attachments and the size and shape of bony eminences.
在脊椎动物中，连接骨骼的肌腱和韧带对于关节的活动性和稳定性至关重要。肌腱和韧带的附着处（即附着点）位于骨骼突起处（即骨突），这些突起的形状和大小取决于生长过程中的机械力和细胞信号。肌腱骨突也为骨骼肌提供机械杠杆作用。成纤维细胞生长因子受体（FGFR）信号在骨骼发育中起着关键作用，Fgfr1 和 Fgfr2 在软骨膜和骨膜中高度表达，而附着点就在这些地方。
我们使用了在肌腱/附着祖细胞（ScxCre）中组合敲除 Fgfr1 和/或 Fgfr2 的转基因小鼠，并测量了骨突的大小和形状。Scx 前体细胞中同时缺失 Fgfr1 和 Fgfr2，但不是单独缺失，会导致出生后骨骼中骨突增大和长骨缩短。此外，Fgfr1/Fgfr2 双条件敲除小鼠的肌腱中胶原纤维大小变化更大，胫骨斜率降低，韧带附着处的细胞死亡增加。这些发现表明 FGFR 信号在调节肌腱/韧带附着处的生长和维持以及骨突的大小和形状方面发挥了作用。
