Grant: Discovery Grants Program - Individual

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.