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）网络已经形成。ECM提供的生化和机械信号被认为指导细胞的命运和功能。我们假设在ECM中编码的信息是由其形成过程中存在的物理化学刺激调制的，并且存储的信息将被细胞感知的时间比刺激存在的时间长得多。我们将在机械张力和骨形态发生蛋白（BMPs）的控制下，在3D微组织培养中构建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作用，并研究衰老对编码和读取过程的影响。我们认为，在骨再生过程中，ECM作为一种年龄依赖性记忆，对机械和生化信号起着相关作用。

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.