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  • Strålberg, FredrikUmeå universitet,Umeå University,Molekylär paradontologi (författare)

Inhibition of lipopolysaccharide-induced osteoclast formation and bone resorption in vitro and in vivo by cysteine proteinase inhibitors

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • FEDERATION AMER SOC EXP BIOL,2017

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/254498
  • https://gup.ub.gu.se/publication/254498URI
  • https://doi.org/10.1189/jlb.3A1016-433RDOI
  • https://lup.lub.lu.se/record/c09dd88f-2f9e-4a59-83e2-d583cf95b08fURI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-136068URI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Inflammation-induced bone destruction is a major treatment target in many inflammatory skeletal diseases. The aim of this study was to investigate if the cysteine proteinase inhibitors cystatin C, fungal cysteine proteinase inhibitor (E-64), and N-benzyloxycarbonyl-arginylleucyl-valyl-glycyl-diazomethane acetate (Z-RLVG-CHN2) can inhibit LPS-induced osteoclast formation. Mouse bone marrow macrophages (BMMs) were isolated and primed with receptor activator of NF-kappa B ligand (RANKL) for 24 h, followed by stimulation with LPS, with and without inhibitors. Adult mice were injected locally with LPS and then treated with E-64 and osteoclast formation assessed by the number of cathepsin K+ multinucleated cells. Cystatin C inhibited LPS-induced osteoclast formation time and concentration dependently (IC50 = 0.3 mu M). The effect was associated with decreased mRNA and protein expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K and of the osteoclastogenic transcription factors c-Fos and NFATc1. LPS-induced osteoclast formation on bone slices was also inhibited by cystatin C, resulting in decreased pit formation and release of bone matrix proteins. Similar data were obtained with E-64 and Z-RLVG-CHN2. Cystatin C was internalized in BMMs stimulated by LPS but not in unstimulated BMMs. Osteoclast formation induced by LPS was dependent on TNF-alpha, and the 3 inhibitors abolished LPS-induced TNF superfamily 2 (gene encoding TNF-alpha; Tnfsf2) mRNA expression without affecting Il1b, Il6, or oncostatin M (Osm) expression. Formation of osteoclasts in the skull bones after local LPS stimulation was inhibited by E-64. It is concluded that cysteine proteinase inhibitors effectively inhibit LPS-induced osteoclast formation in vivo and in vitro by inhibition of TNF-alpha expression. The targeting of cysteine proteinases might represent a novel treatment modality for prevention of inflammatory bone loss. RAHAMSON M, 1988, FEBS LETTERS, V236, P14 RAHAMSON M, 1990, BIOCHEMICAL JOURNAL, V268, P287

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Kassem, AliUmeå universitet,Umeå University,Molekylär paradontologi(Swepub:umu)alka0011 (författare)
  • Kasprzykowski, F.University of Gdansk (författare)
  • Abrahamson, MagnusLund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kkem-mab (författare)
  • Grubb, AndersLund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kkem-agr (författare)
  • Lindholm, Catharina,1967University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xlicat (författare)
  • Lerner, Ulf HUmeå universitet,University of Gothenburg,Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Molekylär paradontologi(Swepub:umu)ulle0001 (författare)
  • Umeå UniversityMolekylär paradontologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Leukocyte Biology: FEDERATION AMER SOC EXP BIOL101:5, s. 1233-12430741-54001938-3673

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