Mechanical strain and BMP-stimulation instruct the extracellular matrix to control stem cell fate decisions: an age-dependent matrix code?

在骨折愈合的早期阶段，一个复杂的细胞外基质(ECM)网络已经组装起来。细胞外基质提供的生化和机械信号被认为是指导细胞命运和功能的信号。我们假设在ECM中编码的信息受到形成过程中存在的物理化学刺激的调制，并且存储的信息将被细胞感觉到的时间比刺激存在的时间要长得多。我们将在机械应变和骨形态发生蛋白(BMPs)的控制下，在三维微组织培养中建立ECM，并进行仔细的机械和生化表征。我们将进一步研究脱细胞基质对骨祖细胞的指导性，并研究老化对编码和阅读过程的影响。我们认为，在骨再生过程中，细胞外基质作为机械和生化信号的年龄依赖性记忆发挥了相关的作用。

Already in the very early phase of bone fracture healing, a complex extracellular matrix (ECM) network is assembled. The biochemical and mechanical signals provided by the ECM are believed to instruct cell fate and function. We hypothesize that the information encoded in the ECM is modulated by the physico-chemical stimuli present during its formation and that the stored information will be sensed by cells much longer than the stimuli were present. We will build ECM in 3D microtissue culture under control of mechanical straining and bone morphogenetic proteins (BMPs) and perform careful mechanical and biochemical characterization. We will furthermore study the instructiveness of decellularized matrices on bone progenitor cells and investigate the influence of ageing on the encoding and reading process. We propose that the ECM plays a relevant role as an age-dependent memory for mechanical and biochemical signals during bone regeneration.