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，有必要提高对骨代谢调节的理解。破骨细胞介导的骨降解和成骨细胞介导的骨形成之间的平衡维持了骨量及其功能。母细胞在骨骼维护中的作用需要调节功能。这些事件在多能间充质干细胞（MSC）分化（称为成骨）过程中得到及时的调节，这些干细胞从MSC分化为增殖性成骨细胞/成骨前细胞和非增殖性骨基质分泌母细胞。为了了解调控OBlast功能的机制，我的研究项目主要集中在瞬时受体电位（TRP）家族离子通道在OBlast功能中的广泛作用。我的中心假设是成骨过程中不同TRP通道的表达模式反映了它们在成熟的每个阶段的特定功能含义。这种新颖的全球概念方法旨在揭示TRP通道在OBlast发育/功能中的作用，将突出TRP与成骨过程中信号通路之间的关键和特定关系。我的中期研究目标是：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，细胞表现出特定的功能特征：1)增殖型与非增殖型，2)多能型与固定型，3)迁移型与非移动型骨基质分泌细胞。我们推测它们的表达将与骨形成过程中特定阶段的功能特征相关；2) TRP表达水平与OBlast功能和分化的关系。我们期望突出TRP通道组，其表达将受到增殖和汇合条件的调节。此外，许多钙依赖的信号分子已被证明在OBlast分化/功能中发挥关键作用。因此，特定通道介导的钙内流应该触发OBlast功能的不同信号传导和基因通路。

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.