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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.
AuthorsAlwin Scharstuhl, Harrie L Glansbeek, Henk M van Beuningen, Elly L Vitters, Peter M van der Kraan, Wim B van den Berg
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 169 Issue 1 Pg. 507-14 (Jul 01 2002) ISSN: 0022-1767 [Print] United States
PMID12077282 (Publication Type: Journal Article)
Chemical References
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Recombinant Proteins
  • Tgfb1 protein, mouse
  • Tgfb3 protein, mouse
  • Tissue Inhibitor of Metalloproteinases
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta3
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • ADAM Proteins
  • ADAMTS5 Protein
  • Adamts5 protein, mouse
  • Collagenases
  • Matrix Metalloproteinase 13
  • Metalloendopeptidases
  • Mmp13 protein, mouse
  • Procollagen N-Endopeptidase
  • Matrix Metalloproteinase 1
  • ADAMTS4 Protein
Topics
  • ADAM Proteins
  • ADAMTS4 Protein
  • ADAMTS5 Protein
  • Animals
  • Arthritis, Experimental (immunology, metabolism, pathology)
  • Blotting, Western
  • Cartilage, Articular (chemistry, drug effects, immunology, pathology)
  • Cell Differentiation (drug effects, immunology)
  • Chondrocytes (drug effects, immunology, pathology)
  • Collagenases (biosynthesis, genetics)
  • Electrophoresis, Polyacrylamide Gel
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 1 (biosynthesis, genetics)
  • Matrix Metalloproteinase 13
  • Metalloendopeptidases (biosynthesis, genetics)
  • Mice
  • Mice, Inbred C57BL
  • Osteoarthritis, Knee (immunology, metabolism, pathology)
  • Osteogenesis (drug effects, immunology)
  • Pichia (enzymology)
  • Procollagen N-Endopeptidase
  • Protein Isoforms (analysis, antagonists & inhibitors, biosynthesis)
  • Protein Serine-Threonine Kinases
  • RNA, Messenger (biosynthesis)
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta (analysis, biosynthesis, physiology)
  • Recombinant Proteins (analysis, biosynthesis, pharmacology)
  • Solubility
  • Tissue Inhibitor of Metalloproteinases (biosynthesis, genetics)
  • Transforming Growth Factor beta (analysis, antagonists & inhibitors, biosynthesis)
  • Transforming Growth Factor beta1
  • Transforming Growth Factor beta3

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