Zelzer Elazar, Blitz Einat, Killian Megan L, Thomopoulos Stavros
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Birth Defects Res C Embryo Today. 2014 Mar;102(1):101-12. doi: 10.1002/bdrc.21056.
The attachment between tendon and bone occurs across a complex transitional tissue that minimizes stress concentrations and allows for load transfer between muscles and skeleton. This unique tissue cannot be reconstructed following injury, leading to high incidence of recurrent failure and stressing the need for new clinical approaches. This review describes the current understanding of the development and function of the attachment site between tendon and bone. The embryonic attachment unit, namely, the tip of the tendon and the bone eminence into which it is inserted, was recently shown to develop modularly from a unique population of Sox9- and Scx-positive cells, which are distinct from tendon fibroblasts and chondrocytes. The fate and differentiation of these cells is regulated by transforming growth factor beta and bone morphogenetic protein signaling, respectively. Muscle loads are then necessary for the tissue to mature and mineralize. Mineralization of the attachment unit, which occurs postnatally at most sites, is largely controlled by an Indian hedgehog/parathyroid hormone-related protein feedback loop. A number of fundamental questions regarding the development of this remarkable attachment system require further study. These relate to the signaling mechanism that facilitates the formation of an interface with a gradient of cellular and extracellular phenotypes, as well as to the interactions between tendon and bone at the point of attachment.
肌腱与骨骼之间的附着通过一种复杂的过渡组织实现，该组织可将应力集中降至最低，并允许肌肉与骨骼之间进行负荷传递。这种独特的组织在损伤后无法重建，导致反复失败的发生率很高，凸显了新临床方法的必要性。本综述描述了目前对肌腱与骨骼附着部位的发育和功能的理解。胚胎附着单元，即肌腱末端及其插入的骨隆起，最近被证明是由一群独特的Sox9和Scx阳性细胞模块化发育而来，这些细胞不同于肌腱成纤维细胞和软骨细胞。这些细胞的命运和分化分别受转化生长因子β和骨形态发生蛋白信号通路调控。然后，肌肉负荷对于组织成熟和矿化是必需的。附着单元的矿化在大多数部位出生后发生，主要受印度刺猬因子/甲状旁腺激素相关蛋白反馈回路控制。关于这个非凡附着系统发育的一些基本问题需要进一步研究。这些问题涉及促进形成具有细胞和细胞外表型梯度的界面的信号机制,以及附着点处肌腱与骨骼之间的相互作用。
