title: Inhibition of p38 mitogen-activated protein kinase down-regulates the inflammatory osteolysis response to titanium particles in a murine osteolysis model.
abstract: The p38 mitogen-activated protein kinase (p38 MAPK) pathway is involved in the osteoclast differentiation. The aim of the study was to investigate whether SB203580, a p38 MAPK inhibitor, inhibits wear-debris-induced inflammatory osteolysis in mice. Forty-five mice were implanted with calvaria bone from syngeneic littermates; then, titanium (Ti) particles were injected into established air pouches to provoke inflammatory osteolysis. At 14 days after bone/Ti implantation, pouch membranes with intact bone implants underwent histological and molecular analysis. SB203580 had less effect on MMP-9 and TNF-α expression under wear-debris-induced conditions. SB203580, by inhibiting the expression of p38 MAPK and phospho-p38 MAPK, inhibited Ti particle wear-debris-induced inflammatory osteolysis. It also remarkably decreased the number of tartrate-resistant acid phosphatase positive cells in Ti-particle-induced pouch tissues. Results suggest that p38 MAPK may be critical in a murine osteolysis model. SB203580 may notably inhibit wear-debris-induced inflammatory osteolysis by down-regulating expression of MMP-9 and TNF-α via the p38 MAPK pathway.
authors: Department of Orthopaedics, The Sixth Affiliated People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 600 Yishan Road, Shanghai 200233, China.
authors: Desheng
authors: D
authors: Chen
authors: Yongyuan
authors: Y
authors: Guo
authors: Xin
authors: X
authors: Mao
authors: Xianlong
authors: X
authors: Zhang
mesh_terms: D000135:Acid Phosphatase / Q000494:pharmacology; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D007527:Isoenzymes / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010014:Osteolysis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D000071681:Tartrate-Resistant Acid Phosphatase; D014025:Titanium / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D007527:Isoenzymes; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium; D048051:p38 Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; C093642:SB 203580