Participation of MicroRNA-34a and RANKL on bone repair induced by poly(vinylidene-trifluoroethylene)/barium titanate membrane.
The poly(vinylidene-trifluoroethylene)/barium titanate (PVDF) membrane enhances in vitro osteoblast differentiation and in vivo bone repair. Here, we hypothesized that this higher bone repair could be also due to bone resorption inhibition mediated by a microRNA (miR)/RANKL circuit. To test our hypothesis, the large-scale miR expression of bone tissue grown on PVDF and polytetrafluoroethylene (PTFE) membranes was evaluated to identify potential RANKL-targeted miRs modulated by PVDF. The animal model used was rat calvarial defects implanted with either PVDF or PTFE. At 4 and 8 weeks, the bone tissue grown on membranes was submitted to a large-scale analysis of miRs by microarray. The expression of miR-34a and some of its targets, including RANKL, were evaluated by real-time polimerase chain reaction and osteoclast activity was detected by tartrate-resistant acid phosphatase (TRAP) staining. Among more than 250 miRs, twelve, including miR-34a, were simultaneously higher expressed (≥2 fold) at 4 and 8 weeks on PVDF. The higher expression of miR-34a was concomitant with a reduced expression of all its evaluated targets, including RANKL. Additionally, more TRAP-positive cells were observed in bone tissue grown on PTFE compared with PVDF in both time points. In conclusion, our results suggest that the higher bone formation induced by PVDF could be, at least in part, triggered by a miR-34a increase and RANKL decrease, which may inhibit osteoclast differentiation and activity, and bone resorption.
a Cell Culture Laboratory , School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil.
Helena B
HB
Lopes
a Cell Culture Laboratory , School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil.
Emanuela P
EP
Ferraz
a Cell Culture Laboratory , School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil.
Adriana L G
AL
Almeida
a Cell Culture Laboratory , School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil.
Pedro
P
Florio
b Institute of Physics and Chemistry, Federal University of Itajubá , Itajubá , Brazil.
Rossano
R
Gimenes
a Cell Culture Laboratory , School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil.
Adalberto L
AL
Rosa
a Cell Culture Laboratory , School of Dentistry of Ribeirão Preto, University of São Paulo , Ribeirão Preto , Brazil.
Marcio M
MM
Beloti
D000818:Animals; D017609:Barium Compounds / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001861:Bone Regeneration; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D015870:Gene Expression; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D008567:Membranes, Artificial; D035683:MicroRNAs / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D053245:RANK Ligand / Q000378:metabolism*; D017208:Rats, Wistar; D014025:Titanium / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*
D017609:Barium Compounds; D006845:Hydrocarbons, Fluorinated; C560944:MIRN34 microRNA, rat; D008567:Membranes, Artificial; D035683:MicroRNAs; D053245:RANK Ligand; D014753:Vinyl Compounds; C522521:poly(vinylidenefluoride-trifluoroethylene); C024547:barium titanate(IV); D014025:Titanium
Bone; RANKL; biomaterial; microRNA; osteoclast