title: Effect of 15-Deoxy-Δ12,14-prostaglandin J2Nanocapsules on Inflammation and Bone Regeneration in a Rat Bone Defect Model.
abstract: BACKGROUND
  15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the major metabolites from prostaglandin D2 in arachidonic acid metabolic pathway, has potential anti-inflammatory properties. The objective of this study was to explore the effects of 15d-PGJ2-loaded poly(D,L-lactide-co-glycolide) nanocapsules (15d-PGJ2-NC) on inflammatory responses and bone regeneration in local bone defect.
  
  
  METHODS
  The study was conducted on 96 Wistar rats from June 2014 to March 2016. Saline, unloaded nanoparticles, free 15d-PGJ2or 15d-PGJ2-NC, were delivered through a collagen vehicle inside surgically created transcortical defects in rat femurs. Interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels in the surrounding soft tissue were analyzed by Western blot and in the defect by quantitative real-time polymerase chain reaction over 14 days. Simultaneously, bone morphogenetic protein-6 (BMP-6) and platelet-derived growth factor-B (PDGF-B) messenger RNA (mRNA) in the defect were examined. New bone formation and EphrinB2 and osteoprotegerin (OPG) protein expression in the cortical defect were observed by Masson's Trichrome staining and immunohistochemistry over 28 days. Data were analyzed by one-way analysis of variance. Least-significant difference and Dunnett's T3 methods were used with a bilateral P< 0.05.
  
  
  RESULTS
  Application of l5d-PGJ2-NC (100 μg/ml) in the local bone defect significantly decreased IL-6, IL-1β, and TNF-α mRNA and protein, compared with saline-treated controls (P < 0.05). l5d-PGJ2-NC upregulated BMP-6 and PDGF-B mRNA (P < 0.05). New bone formation was observed in the cortical defect in l5d-PGJ2-NC-treated animals from 7th day onward (P < 0.001). Expression of EphrinB2 and OPG presented early on day 3 and persisted through day 28 in 15d-PGJ2-NC group (P < 0.05).
  
  
  CONCLUSIONS
  Stable l5d-PGJ2-NC complexes were prepared that could attenuate IL-6, IL-1β, and TNF-α expression, while increasing new bone formation and growth factors related to bone regeneration.
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Chen
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Wei-Lian
authors.initials: WL
authors.lastname: Sun
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Lei
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Pei-Hui
authors.initials: PH
authors.lastname: Ding
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Tan
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Xiao-Tao
authors.initials: XT
authors.lastname: Chen
authors.affiliation: Department of Oral Medicine, The Second Affiliated Hospital of School of Medicine of Zhejiang University, Hangzhou, Zhejiang 310009, China.
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Wu
mesh_terms: D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C477819:15-deoxyprostaglandin J2; D055418:Bone Morphogenetic Protein 6; D053583:Interleukin-1beta; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D015230:Prostaglandin D2