Expression and functions of transient receptor potential (TRP) channels during differentiation of bone-forming osteoblast

鉴于骨在全球健康中的重要作用，有必要更好地了解骨代谢的调节。通过破骨细胞介导的骨降解和成骨细胞(成骨细胞)介导的骨形成之间的平衡来维持骨量及其功能。成骨细胞在骨骼维持中的作用需要调节功能。这些事件在其从多能间充质干细胞(MSC)向承诺的增殖性成骨细胞/前成骨细胞和非增殖性骨基质分泌的成骨细胞分化(称为成骨)过程中受到及时的调控。为了了解OBLAST功能的调控机制，我的研究计划集中在瞬时受体电位(Trp)家族的离子通道在一系列OBLAST功能中的作用。我的中心假设是，不同的Trp通道在成骨过程中的表达模式反映了它们在成骨成熟的每个阶段的特定功能含义。这一新的全球概念性方法旨在揭示Trp通道在成骨细胞发育/功能中的作用，将突出TRPs和信号通路之间在成骨形成中的关键和特定关系。本研究的中期目标是：1)建立Trp通道在成骨过程中的表达模式。在成骨的每个阶段，细胞都表现出特定的功能特征：1)增殖表型与非增殖表型；2)多能表型与承诺表型；3)迁徙表型与非运动性骨基质分泌细胞。我们推测，它们的表达将与成骨过程中特定阶段的功能特征相关；2)TRP的表达水平与成骨细胞的功能和分化有关。我们预计将突出一组Trp通道，其表达将受到增殖和融合条件的调节。此外，许多钙依赖的信号分子在成骨细胞分化/功能中发挥关键作用。因此，通过特定的通道介导的钙离子内流应该触发不同的信号和基因途径来发挥成骨细胞的功能。

Given the important role of bone in global health, there is a need for improved understanding of the regulation of bone metabolism. Bone mass and its functions are preserved by the balance between the bone degradation mediated by osteoclast and bone formation mediated by osteoblast (OBlasts). The role for OBlasts in bone maintenance requires tuned regulation of functions. These events are timely regulated throughout their differentiation (called osteopoiesis) from pluripotent mesenchymal stem cells (MSC) into committed proliferating osteoprogenitors/preosteoblasts and non-proliferating bone matrix-secreting OBlasts. To gain knowledge on mechanisms regulating OBlast functions, my research program has focused on the roles of ion channels of the transient receptor potential (TRP) family in a wide array of OBlast functions. My central hypothesis is that the expression pattern of distinct TRP channels during osteopoiesis reflects their specific functional implications in each stage of this maturation. This novel and global conceptual approach aimed to unravel the roles of TRP channels in OBlast development/functions will highlight critical and specific relationships between TRPs and signaling pathways in osteopoiesis. The mid-term objectives of my research are to: 1) Establish the expression pattern of TRP channels along osteopoiesis. At each stage of osteopoiesis, cells show specific functional features: i) proliferating vs non-proliferating phenotypes, ii) pluripotent vs committed phenotypes and iii) migrating vs non-motile bone matrix-secreting cells. We speculate that their expression will correlate with stage-specific functional features along osteopoiesis; 2) Associate TRP expression level with OBlast functions and differentiation. We anticipate highlighting group of TRP channels whose expression will be regulated by proliferation and confluence conditions. Also, numerous calcium-dependent signaling molecules have been show to play key roles in OBlast differentiation/functions. Therefore, calcium influx mediated by specific channels should trigger distinct signaling and gene pathways for OBlast functions.