title: miR-126 regulates platelet-derived growth factor receptor-α expression and migration of primary human osteoblasts.
abstract: Adequate vascularization is an essential requirement for bone development, fracture healing and bone tissue engineering. We have previously described the coculture of primary human osteoblasts (hOBs) and human endothelial cells (HUVECs), designed to investigate the interactions between these cells. In this system, we showed that cocultivation of these two cell types leads to a downregulation of platelet-derived growth factor receptor-α (PDGFR-α) in hOBs, which was a consequence of reduced mRNA stability. In the current study we investigated the possible involvement of microRNAs in this process. Firstly, we performed a microarray analysis of osteoblastic miRNAs following cocultivation with HUVECs, revealing an upregulation of miR-126. This result was confirmed by RT-qPCR, and we observed that the increase is dependent on direct cell-to-cell contacts. Gain-of-function and loss-of-function experiments showed that miR-126 is a negative regulator of PDGFR-α mRNA. Additionally, migration of hOBs was inhibited by miR-126 overexpression and stimulated by miR-126 inhibition. Addition of PDGFR-α blocking antibody to hOB culture also inhibited hOB migration. There was no effect of miR-126 modulation on osteoblast proliferation, apoptosis rate or differentiation. In conclusion, we report that the miR-126/PDGFR-α system regulates the migratory behavior of human osteoblasts, without exerting effects on cell survival and differentiation.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schmidt
authors.forename: Filip
authors.initials: F
authors.lastname: Simunovic
authors.forename: Sandra
authors.initials: S
authors.lastname: Strassburg
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pfeifer
authors.forename: G Björn
authors.initials: GB
authors.lastname: Stark
authors.forename: Günter
authors.initials: G
authors.lastname: Finkenzeller
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D017479:Receptors, Platelet-Derived Growth Factor