Local suppression of pro-inflammatory cytokines and the effects in BMP-2-induced bone regeneration.
The objective of this study is to investigate the effect of local inflammation suppression on the bone regeneration. Gelatin hydrogels incorporating mixed immunosuppressive triptolide-micelles and bone morphogenic protein-2 (BMP-2) were prepared. The controlled release of both the triptolide and BMP-2 from the hydrogels was observed under in vitro and in vivo conditions. When either J774.1 macrophage-like or MC3T3-E1 osteoblastic cells were cultured in the hydrogels incorporating mixed 2.5, 5 or 10 mg of triptolide-micelles and BMP-2, the expression level of pro- and anti-inflammatory cytokines including interleukin (IL)-6 and IL-10 was down-regulated, but the alkaline phosphatase (ALP) activity was promoted compared with those of hydrogels incorporating BMP-2 without triptolide-micelles. When implanted into a critical-sized bone defect of rats, the hydrogels incorporating mixed 2.5 or 5 mg of triptolide-micelles and BMP-2 showed significantly lower number of neutrophils, lymphocytes, macrophages or dendritic and mast cells infiltrated into the defect, and lower expression level of IL-6, TNF-α, and IL-10 than those incorporating BMP-2 without triptolide-micelles. The reduced local inflammation responses at the defects implanted with the hydrogels incorporating mixed 2.5 or 5 mg of triptolide-micelles and BMP-2 subsequently enhanced the bone regeneration thereat. It is concluded that the proper local modulation of inflammation responses is a promising way to achieve the enhanced bone regeneration.
Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Juthamas
J
Ratanavaraporn
Hiroyuki
H
Furuya
Yasuhiko
Y
Tabata
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004224:Diterpenes / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008823:Micelles; D010616:Phenanthrenes / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D055396:Bone Morphogenetic Protein 2; D016207:Cytokines; D004224:Diterpenes; D004852:Epoxy Compounds; D020100:Hydrogels; D008823:Micelles; D010616:Phenanthrenes; C001899:triptolide; D005780:Gelatin