title: [Delta12-prostaglandinJ2-nano capsule up-regulates growth factor expression and enhances bone regeneration in rats].
abstract: OBJECTIVE
  To investigate the effect of local delivery of delta12-prostaglandinJ2-loaded poly (lactic-co-glycolic acid) (Δ(12)-PGJ2-NC) on growth factors expression and bone formation.
  
  
  METHODS
  Δ(12)-PGJ2-NC was prepared by the emulsion solvent diffusion method. The physical and chemical properties of the nanoparticles were evaluated by particle size analysis, transmission electron microscopy, drug-loading ratio and the in vitro release study. Then standardized transcortical defect (5.0 mm × 1.5 mm) was conducted in the femur of 48 male Wistar rats which were randomly divided into four groups (n = 12), S, K, F, and N. Thirty microliter of saline (S), unloaded nanoparticles (K), Δ(12)-PGJ2 (F) and Δ(12)-PGJ2-NC(N) in a collagen vehicle were delivered inside a titanium chamber fixed over the defect. Then, four subgroups were randomly divided in each group named as D3, D7, D14, and D28 (n = 3) according to the days 3, 7, 14, and 28 after the surgery. At days 3, 7, 14, and 28, the mRNA expression of the bone morphogenetic protein-6 (BMP-6), platelet-derived growth factor-B (PDGF-B) in defect aera was analyzed by real time quantitive-polymerase blotting. HE staining was employed to reveal new bone formation in weeks 2 and 4.
  
  
  RESULTS
  Δ(12)-PGJ2-NC appeared opalescent white and remained relatively stable, with an average particle size of (135.2 ± 0.85) nm. The images from transmission electron microscopy showed that Δ(12)-PGJ2-NC was spherical in shape and homogeneously distributed. The encapsulation efficiency of Δ(12)-PGJ2 with the poly (lactic-co-glycolic acid) (PLGA) nanocapsules was about 92%. The in vitro release of Δ(12)-PGJ2-NC at 37 °C showed a sustained fashion and the average accumulated amount was 30%, 52%, 77%, 91%, and 98% respectively, at 0.5, 1, 2, 4 and 6 h. Compared with the animals treated with saline, after dose of 100 mg/L Δ(12)-PGJ2 and Δ(12)-PGJ2-NC apllication, the mRNA expression level of BMP-6, PDGF-B increased significantly (P < 0.05, P < 0.001). The protein expression of BMP-6, Ephrin-B2 also was up-regulated. Histomorphometry revealed that new bone formation increased at the same dose of 100 mg/L. But the unloaded nanoparticles did not have the same effect (P > 0.05).
  
  
  CONCLUSIONS
  A stable Δ(12)-PGJ2 loaded nanoparticle was successfully prepared. Δ(12)-PGJ2-NC may upregulate the expression of BMP-6, PDGF-B and Ephrin-B2, and promote new bone formation in bone defect area.
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Weilian
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Peihui
authors.initials: P
authors.lastname: Ding
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China; Email: wym731128@126.com.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D036388:Ephrin-B2 / Q000235:genetics / Q000378:metabolism; D005269:Femur / Q000187:drug effects* / Q000601:surgery; D019344:Lactic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D053769:Nanocapsules / Q000008:administration & dosage; D053758:Nanoparticles / Q000008:administration & dosage; D010316:Particle Size; D011100:Polyglycolic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015230:Prostaglandin D2 / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C525818:Bmp6 protein, rat; D055418:Bone Morphogenetic Protein 6; D036388:Ephrin-B2; D053769:Nanocapsules; D012333:RNA, Messenger; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; D020797:Receptor, Platelet-Derived Growth Factor beta; D015230:Prostaglandin D2