Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Dev Cell. 2009 Dec;17(6):861-73. doi: 10.1016/j.devcel.2009.10.010.
During the assembly of the musculoskeletal system, bone ridges provide a stable anchoring point and stress dissipation for the attachment of muscles via tendons to the skeleton. In this study, we investigate the development of the deltoid tuberosity as a model for bone ridge formation. We show that the deltoid tuberosity develops through endochondral ossification in a two-phase process: initiation is regulated by a signal from the tendons, whereas the subsequent growth phase is muscle dependent. We then show that the transcription factor scleraxis (SCX) regulates Bmp4 in tendon cells at their insertion site. The inhibition of deltoid tuberosity formation and several other bone ridges in embryos in which Bmp4 expression was blocked specifically in Scx-expressing cells implicates BMP4 as a key mediator of tendon effects on bone ridge formation. This study establishes a mechanistic basis for tendon-skeleton regulatory interactions during musculoskeletal assembly and bone secondary patterning.
在运动系统的装配过程中，骨嵴通过肌腱将肌肉附着在骨骼上，为其提供稳定的锚固点和应力耗散。在这项研究中，我们以三角肌粗隆的发育为例来研究骨嵴的形成。我们发现三角肌粗隆通过软骨内骨化在两个阶段发育：起始由来自肌腱的信号调控，而随后的生长阶段则依赖于肌肉。然后我们发现，转录因子 Scleraxis（SCX）在肌腱细胞的插入部位调节 Bmp4 的表达。在 Scx 表达细胞中特异性阻断 Bmp4 表达的胚胎中，三角肌粗隆的形成和其他几个骨嵴的形成受到抑制，这表明 BMP4 是肌腱对骨嵴形成影响的关键介质。这项研究为运动系统装配过程中肌腱-骨骼调节相互作用以及骨骼二级模式形成建立了一个机制基础。
