Neuropilin 2-gemedieerde semaphorin signaalcasacde in bot. English title Neuropilin 2-mediated semaphorin signaling in bone.

Osteoporosis and osteoporosis-related fractures remain an important public health issue. Most available treatments focus on inhibiting bone resorption whereas bone anabolic therapies are limited. A comprehensive understanding of the intercellular communication within the bone microenvironment is crucial for the development of novel therapies that not only inhibit bone resorption but also enhance formation. Recent studies indicate that different semaphorin proteins are involved in normal bone homeostasis and in bone pathology by mediating cross-talk between bone forming osteoblasts and bone resorbing osteoclasts. Class 3 semaphorins exert their non-redundant functions by binding to the neuropilin (Nrp) receptors, which subsequently recruit signal-transducing plexin molecules. To date, the expression of Nrp2 and its possible function in bone remain to be identified. Preliminary data demonstrate that Nrp2 knockout mice have a reduced bone mass that is accompanied by increased osteoclast and reduced osteoblast numbers, suggesting that Nrp2 has a dual role. In the present project, we will decipher whether this bone phenotype is the result of a disturbed cross-talk between osteoblasts and osteoclasts. We aim at identifying the ligand for Nrp2 in bone as well as the composition and down-stream signaling of the holoreceptor complex. Finally, we will investigate whether Nrp2 signaling is involved in fracture repair. This research may lead to a novel therapy that targets Nrp2- mediated semaphorin signaling and not only inhibits bone resorption but also enhances bone formation.