PMID- 27638499
OWN - NLM
STAT- MEDLINE
DCOM- 20171129
LR  - 20220316
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 36
IP  - 5
DP  - 2016 Oct
TI  - Blockade of NF-kappaB and MAPK pathways by ulinastatin attenuates wear 
      particle-stimulated osteoclast differentiation in vitro and in vivo.
LID - e00399
AB  - Ulinastatin, a urinary trypsin inhibitor (UTI), is widely used to clinically 
      treat lipopolysaccharide (LPS)-related inflammatory disorders recently. Adherent 
      pathogen-associated molecular patterns (PAMPs), of which LPS is the best-studied 
      and classical endotoxin produced by Gram-negative bacteria, act to increase the 
      biological activity of osteopedic wear particles such as polymethyl-methacrylate 
      (PMMA) and titanium particles in cell culture and animal models of implant 
      loosening. The present study was designed to explore the inhibitory effect of UTI 
      on osteoclastogenesis and inflammatory osteolysis in LPS/PMMA-mediated Raw264.7 
      cells and murine osteolysis models, and investigate the potential mechanism. The 
      in vitro study was divided into the control group, LPS-induced group, 
      PMMA-stimulated group and UTI-pretreated group. UTI (500 or 5000 units/ml) 
      pretreatment was followed by PMMA (0.5 mg/ml) with adherent LPS. The levels of 
      inflammatory mediators including tumour necrosis factor-alpha (TNF-alpha), 
      matrixmetallo-proteinases-9 (MMP-9) and interleukin-6 (IL-6), receptor activation 
      of nuclear factor NF-kappaB (RANK), and cathepsin K were examined and the amounts of 
      phosphorylated I-kappaB, MEK, JNK and p38 were measured. In vivo study, murine 
      osteolysis models were divided into the control group, PMMA-induced group and 
      UTI-treated group. UTI (500 or 5000 units/kg per day) was injected 
      intraperitoneally followed by PMMA suspension with adherent LPS (2x10(8) 
      particles/25 mul) in the UTI-treated group. The thickness of interfacial membrane 
      and the number of infiltrated inflammatory cells around the implants were 
      assessed, and bone mineral density (BMD), trabecular number (Tb.N.), trabecular 
      thickness (Tb.Th.), trabecular separation (Tb.Sp.), relative bone volume over 
      total volume (BV/TV) of distal femur around the implants were calculated. Our 
      results showed that UTI pretreatment suppressed the secretion of proinflammatory 
      cytokines including MMP-9, IL-6, TNF-alpha, RANK and cathepsin K through 
      down-regulating the activity of nuclear factor kappa B (NF-kappaB) and MAPKs partly 
      in LPS/PMMA-mediated Raw264.7 cells. Finally, UTI treatment decreased the 
      inflammatory osteolysis reaction in PMMA-induced murine osteolysis models. In 
      conclusion, these results confirm the anti-inflammatory potential of UTI in the 
      prevention of particle disease.
CI  - (c) 2016 The Author(s).
FAU - Ru, Jiang-Ying
AU  - Ru JY
AD  - Department of Orthopedics, The First People's Hospital of Yangzhou City, Second 
      Clinical School of Yangzhou University, Yangzhou 225000, China.
FAU - Xu, Hai-Dong
AU  - Xu HD
AD  - Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing 210002, China.
FAU - Shi, Dai
AU  - Shi D
AD  - Department of Orthopedics, The First People's Hospital of Yangzhou City, Second 
      Clinical School of Yangzhou University, Yangzhou 225000, China.
FAU - Pan, Jun-Bo
AU  - Pan JB
AD  - Department of Orthopedics, The First People's Hospital of Yangzhou City, Second 
      Clinical School of Yangzhou University, Yangzhou 225000, China.
FAU - Pan, Xiao-Jin
AU  - Pan XJ
AD  - Department of Orthopedics, The First People's Hospital of Yangzhou City, Second 
      Clinical School of Yangzhou University, Yangzhou 225000, China.
FAU - Wang, Yan-Fen
AU  - Wang YF
AD  - Department of Pathology, The First People's Hospital of Yangzhou City, Second 
      Clinical School of Yangzhou University, Yangzhou 225000, China 
      wangyanfen315@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161027
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Glycoproteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Pathogen-Associated Molecular Pattern Molecules)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - OR3S9IF86U (urinastatin)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Glycoproteins/*administration & dosage
MH  - Inflammation/chemically induced/*drug therapy/pathology
MH  - Lipopolysaccharides/toxicity
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/biosynthesis
MH  - NF-kappa B/biosynthesis
MH  - Osteoclasts/*drug effects
MH  - Osteogenesis/*drug effects
MH  - Osteolysis/chemically induced/*drug therapy/pathology
MH  - Pathogen-Associated Molecular Pattern Molecules
MH  - RAW 264.7 Cells
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/biosynthesis
PMC - PMC5091469
OTO - NOTNLM
OT  - aseptic loosening (AL)
OT  - lipopolysaccharide (LPS)
OT  - mitogen activated protein kinase (MAPK)
OT  - nuclear factor kappa B (NF-kappaB)
OT  - osteoclast
OT  - osteolysis
OT  - polymethyl-methacrylate (PMMA)
OT  - ulinastatin
EDAT- 2016/10/30 06:00
MHDA- 2017/12/01 06:00
PMCR- 2016/10/01
CRDT- 2016/09/18 06:00
PHST- 2016/07/05 00:00 [received]
PHST- 2016/09/15 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/12/01 06:00 [medline]
PHST- 2016/09/18 06:00 [entrez]
PHST- 2016/10/01 00:00 [pmc-release]
AID - BSR20160234 [pii]
AID - e00399 [pii]
AID - 10.1042/BSR20160234 [doi]
PST - epublish
SO  - Biosci Rep. 2016 Oct 27;36(5):e00399. doi: 10.1042/BSR20160234. Print 2016 Oct.