title: Nrp2 deficiency leads to trabecular bone loss and is accompanied by enhanced osteoclast and reduced osteoblast numbers.
abstract: Neuropilin 1 (Nrp1) and Nrp2 are transmembrane receptors that can bind class 3 semaphorins (Sema3A-G) in addition to VEGF family members to play important roles in axonal guidance, vascularization and angiogenesis, as well as immune responses. Moreover, recent evidence implicates Sema3A/Nrp-mediated signaling in bone regulation. However, to date the expression of Nrp2 in bone has not been investigated and a possible role for Nrp2 in the maintenance of bone homeostasis in vivo remains unexplored. Here we show that Nrp2, together with its possible coreceptors (Plexin A family members and Plexin D1) and class 3 semaphorin ligands, were expressed during in vitro osteogenic differentiation of bone marrow stromal cells. Moreover, Nrp2 transcript and protein levels were highly induced in hematopoietic bone marrow cell-derived osteoclast cultures. Osteoblastic as well as osteoclastic Nrp2 expression was confirmed by immunohistochemistry of the long bones of mice. Interestingly, Nrp2 knockout mice were characterized by a low bone mass phenotype which was accompanied by an increased number of osteoclasts and a decreased osteoblast count. Collectively, these data point to a physiological role for Nrp2 in bone homeostasis.
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, Bus 902, 3000 Leuven, Belgium. lieve.verlinden@med.kuleuven.be
authors.forename: Lieve
authors.initials: L
authors.lastname: Verlinden
authors.forename: Carsten
authors.initials: C
authors.lastname: Kriebitzsch
authors.forename: Ine
authors.initials: I
authors.lastname: Beullens
authors.forename: Biauw Keng
authors.initials: BK
authors.lastname: Tan
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.forename: Annemieke
authors.initials: A
authors.lastname: Verstuyf
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D039943:Neuropilin-2