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Project

Identification of molecular regulators of osteoprogenitor recruitment and osteo-angiogenic coupling during bone formation using developmental models and gene expression profiling.

Fetal bone development as well as homeostatic bone renewal and regenerative fracture healing require osteoprogenitors to be recruited to sites of bone formation and involve a tight spatiotemporal coupling between osteogenesis and angiogenesis. The synchrony observed between these processes in previous research suggests an intense crosstalk between osteoprogenitors and endothelial cells. In fact, skeletal progenitors are increasingly recognized as perivascular cells intimately associating with blood vessels, with functions conceivably relating to bone formation and hematopoietic stem cell support. Here we aim to determine (1) the genetic signature of osteoprogenitor-specific functions in a setup designed to include the cells’ capacity to traffic into developing bones along with blood vessels, and (2) molecular players mediating the osteo-angiogenic crosstalk, by means of RNA-Seq based gene expression profiling. A functional analysis pipeline including in vitro, ex vivo and in vivo assays is used to identify molecules and mechanisms that promote skeletal development, bone formation and fracture healing by regulating osteoprogenitor recruitment and osteo-angiogenic coupling. The findings of this project have the potential to extend the basic knowledge about general mechanisms of cell and developmental biology and of skeletal and hematopoietic niche physiology, and at the same time might be of clinical relevance by ultimately being translated into osteo-anabolic therapies.

Date:1 Oct 2015 →  30 Sep 2018
Keywords:molecular regulators, osteoprogenitor recruitment, osteo-angiogenic coupling, bone formation
Disciplines:Orthopaedics