title: Inhibition of endogenous TGF-beta during experimental osteoarthritis prevents osteophyte formation and impairs cartilage repair.
abstract: Osteoarthritis has as main characteristics the degradation of articular cartilage and the formation of new bone at the joint edges, so-called osteophytes. In this study enhanced expression of TGF-beta1 and -beta3 was detected in developing osteophytes and articular cartilage during murine experimental osteoarthritis. To determine the role of endogenous TGF-beta on osteophyte formation and articular cartilage, TGF-beta activity was blocked via a scavenging soluble TGF-beta-RII. Our results clearly show that inhibition of endogenous TGF-beta nearly completely prevented osteophyte formation. In contrast, treatment with recombinant soluble TGF-beta-RII markedly enhanced articular cartilage proteoglycan loss and reduced the thickness of articular cartilage. In conclusion, we show for the first time that endogenous TGF-beta is a crucial factor in the process of osteophyte formation and has an important function in protection against cartilage loss.
authors.affiliation: Rheumatology Research Laboratory, Department of Rheumatology, University Medical Center, Nijmegen, The Netherlands. a.scharstuhl@ncmls.kun.nl
authors.forename: Alwin
authors.initials: A
authors.lastname: Scharstuhl
authors.forename: Harrie L
authors.initials: HL
authors.lastname: Glansbeek
authors.forename: Henk M
authors.initials: HM
authors.lastname: van Beuningen
authors.forename: Elly L
authors.initials: EL
authors.lastname: Vitters
authors.forename: Peter M
authors.initials: PM
authors.lastname: van der Kraan
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
mesh_terms: D051722:ADAM Proteins; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D019902:Chondrocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects / Q000276:immunology; D010843:Pichia / Q000201:enzymology; D011348:Procollagen N-Endopeptidase; D020033:Protein Isoforms / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology; D012995:Solubility; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C508961:Tgfb1 protein, mouse; C509045:Tgfb3 protein, mouse; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; C507081:Mmp13 protein, mouse; D011348:Procollagen N-Endopeptidase; D020781:Matrix Metalloproteinase 1; D000071121:ADAMTS4 Protein