Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis.

Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Research Abstract Details 

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Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Abstract Text:

Alwin Scharstuhl,Elly L Vitters,Peter M van der Kraan,Wim B van den Berg,

OBJECTIVE: Osteoarthritis (OA) is a joint disease characterized by osteophyte development, fibrosis, and articular cartilage damage. Effects of exogenous transforming growth factor beta (TGFbeta) isoforms and bone morphogenetic proteins (BMPs) suggest a role for these growth factors in the pathogenesis of OA. The aim of this study was to elucidate the role of endogenous TGFbeta and BMP during papain-induced OA-like changes in mice. METHODS: We used adenoviral overexpression of TGFbeta and BMP antagonists to block growth factor signaling. An adenovirus expressing a secreted, pan-specific TGFbeta antagonist called murine latency-associated peptide 1 (mLAP-1) was used. In addition, we used intracellular inhibitory Smad6 as a BMP antagonist and Smad7 as a TGFbeta/BMP inhibitor. Papain was injected into the knee joints of C57BL/6 mice to induce osteophyte development, synovial thickening, and articular cartilage proteoglycan (PG) loss. RESULTS: Intraarticular injection of papain caused increased protein expression of several TGFbeta and BMP isoforms in synovium and cartilage. Adenovirus transfection into the joint resulted in a strong expression of the transgenes in the synovial lining. Overexpression of mLAP-1, Smad6, and Smad7 led to a significant reduction in osteophyte formation compared with that in controls. Smad6 and Smad7 overexpression also significantly decreased synovial thickening. Furthermore, the secreted TGFbeta inhibitor mLAP-1 increased articular cartilage PG loss. CONCLUSION: Our results indicate a pivotal role of endogenous TGFbeta in the development of osteophytes and synovial thickening, implicating endogenous TGFbeta in the pathogenesis of OA. In contrast, the prevention of cartilage damage by endogenous TGFbeta signifies the protective role of TGFbeta in articular cartilage. This is the first study to demonstrate that endogenous BMPs are involved in osteophyte formation and synovial thickening in experimental OA.

Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Publishing Authors By Initials

A Scharstuhl,EL Vitters,PM van der Kraan,WB van den Berg,

For similar genetic structures: genome: genome components: genes: transgenes research abstracts see: genetic structures: genome: genome components: genes: transgenes research

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Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Arthritis and rheumatism

VOLUME: 48

Page Numbers: 3442-51

Journal Abbreviation: Arthritis Rheum.

ISSN: 0004-3591

DAY: 19

MONTH: Dec

YEAR: 2003

Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Information

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LANGUAGE: eng

NlmUniqueID: 370605

Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Keywords Mesh Terms:

KEYWORDS: Transgenes

MESH TERMS: physiology

Chemical & Substance for Abstract: Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis. Information

Substance Name: Papain

Registry Number: EC 3.4.22.2

Grant and Affiliation Information for Reduction of osteophyte formation and synovial thickening by adenoviral overexpression of transforming growth factor beta/bone morphogenetic protein inhibitors during experimental osteoarthritis.

AFFILIATION: University Medical Center Nijmegen, Nijmegen, The Netherlands.

Country: United States

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MEDLINETA: Arthritis Rheum

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