A model of inflammatory arthritis highlights a role for oncostatin M in pro-inflammatory cytokine-induced bone destruction via RANK/RANKL.
Oncostatin M is a pro-inflammatory cytokine previously shown to promote marked cartilage destruction both in vitro and in vivo when in combination with IL-1 or tumour necrosis factor alpha. However, the in vivo effects of these potent cytokine combinations on bone catabolism are unknown. Using adenoviral gene transfer, we have overexpressed oncostatin M in combination with either IL-1 or tumour necrosis factor alpha intra-articularly in the knees of C57BL/6 mice. Both of these combinations induced marked bone damage and markedly increased tartrate-resistant acid phosphatase-positive multinucleate cell staining in the synovium and at the front of bone erosions. Furthermore, there was increased expression of RANK and its ligand RANKL in the inflammatory cells, in inflamed synovium and in articular cartilage of knee joints treated with the cytokine combinations compared with expression in joints treated with the cytokines alone or the control. This model of inflammatory arthritis demonstrates that, in vivo, oncostatin M in combination with either IL-1 or tumour necrosis factor alpha represents cytokine combinations that promote bone destruction. The model also provides further evidence that increased osteoclast-like, tartrate-resistant acid phosphatase-positive staining multinucleate cells and upregulation of RANK/RANKL in joint tissues are key factors in pathological bone destruction.
Hui
Wang
W
Musculoskeletal Research Group, The Medical School, University of Newcastle, Newcastle upon Tyne, UK. wang.hui@ncl.ac.uk
Cawston
Tim E
TE
Richards
Carl D
CD
Rowan
Andrew D
AD
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002352:Carrier Proteins / Q000502:physiology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000633:toxicity; D015726:Giant Cells / Q000473:pathology; D006965:Hyperplasia; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology* / Q000633:toxicity; D007719:Knee Joint / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D053683:Oncostatin M; D010010:Osteoclasts / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011993:Recombinant Fusion Proteins / Q000502:physiology / Q000633:toxicity; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology* / Q000633:toxicity
D002352:Carrier Proteins; D016207:Cytokines; D007375:Interleukin-1; D008562:Membrane Glycoproteins; C508352:Osm protein, mouse; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011993:Recombinant Fusion Proteins; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M