Osteoarthritic Human Cartilage Is More Sensitive to Transforming Growth Factor   Than Is Normal Cartilage

Lafeber, Floris P. J. G.; Kraan, P. M. Vander; Huber-Bruning, O.; Berg, W. B. Vanden Berg; Bijlsma, J. W. J.

doi:10.1093/rheumatology/32.4.281

Cited by 59 publications

(41 citation statements)

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“…Several lines of evidence suggest an important role for TGF-␤ in cartilage maintenance. We and others (14,15,36) showed that TGF-␤ can increase PTG synthesis in normal and OA chondrocytes in vivo and in vitro. Furthermore, local administration of TGF-␤ can suppress IL-1-induced matrix degradation (17,37), probably via down-regulating MMPs (38, 39) and/or increasing the level of TIMPs (38,40).…”

Section: Discussionmentioning

confidence: 71%

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Scharstuhl

Glansbeek

Beuningen

et al. 2002

The Journal of Immunology

218

157

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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-β1 and -β3 was detected in developing osteophytes and articular cartilage during murine experimental osteoarthritis. To determine the role of endogenous TGF-β on osteophyte formation and articular cartilage, TGF-β activity was blocked via a scavenging soluble TGF-β-RII. Our results clearly show that inhibition of endogenous TGF-β nearly completely prevented osteophyte formation. In contrast, treatment with recombinant soluble TGF-β-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-β is a crucial factor in the process of osteophyte formation and has an important function in protection against cartilage loss.

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Section: Discussionmentioning

confidence: 71%

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Scharstuhl

Glansbeek

Beuningen

et al. 2002

The Journal of Immunology

218

157

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“…In cartilage sections from normal joints, only a few chondrocytes expressed TGF-, whereas in an inflamed arthritic joint the staining of chondrocytes for TGF-s and their receptors was intense. It is known that chondrocytes respond to TGF-by increased proteoglycan (PG) synthesis [30,31], and that normal cartilage needs to be stimulated with TGF-for a few days before PG synthesis is apparent [32]. It is tempting to speculate that the expression of TGF-s on chondrocytes in an inflamed joint acts in an autocrine manner, counteracting destruction by enhancing the synthesis of PG.…”

Section: Discussionmentioning

confidence: 99%

Dynamic expression of transforming growth factor-betas (TGF-β) and their type I and type II receptors in the synovial tissue of arthritic rats

Müssener

Funa

Kleinau

et al. 1997

Clinical and Experimental Immunology

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A well characterized animal model that shares many characteristic features with rheumatoid arthritis (RA) is collagen‐induced arthritis (CIA) in DA rats. Recent studies have demonstrated that TGF‐β, a multifunctional cytokine, is an important modulator of the immune response in CIA, and possibly also in RA. In this study we have investigated the expression of the precursor forms of TGF‐β1, TGF‐β2, TGF‐β3, as well as TGF‐β type I receptor (TGF‐βRI) and TGF‐β type II receptor (TGF‐βRII) in the synovial tissue of arthritic rats during the course of the disease. By using immunohistochemical techniques, an abundant expression of all three TGF‐β isoforms and their receptors was observed in the arthritic synovia, an expression that increased with time after onset of disease. Antibodies to TGF‐β1, TGF‐β2, TGF‐βRI and TGF‐βRII stained blood vessels intensively, already at the early onset of inflammation, whereas the synovial lining layer and chondrocytes expressed strong immunoreactivity later on in the inflammatory process. The most intense staining with these antibodies was detected in fibroblasts within fibrotic tissue, in particular at the cartilage–pannus junction. Interestingly, TGF‐β3 only stained macrophage‐like cells and chondrocytes in the synovia. The data suggest that the abundant expression of TGF‐β1, TGF‐β2, TGF‐β3 as well as TGF‐βRI and TGF‐βRII in the synovia, is of pathogenic importance in the development of CIA, although the question of how the different TGF‐β isoforms may enhance or counteract different arthritogenic events remains open.

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“…Therefore, a feedback loop may exist in the early stages of OA in cartilage that favors the TGF␤1 opposing effect versus IL-1. This is reinforced by the fact that chondrocytes have been shown to be more reactive to TGF␤1 in that phase of the disease, in terms of proteoglycan synthesis, for example (47). Later on, when cartilage becomes heavily eroded (fibrillated stage), the chondrocytes acquire a different metabolic behavior and do not respond in the same way to cytokines and growth factors.…”

Section: Discussionmentioning

confidence: 99%

Mediation of interleukin‐1β–induced transforming growth factor β1 expression by activator protein 4 transcription factor in primary cultures of bovine articular chondrocytes: Possible cooperation with activator protein 1

Andriamanalijaona¹,

Félisaz²,

Kim

et al. 2003

Arthritis & Rheumatism

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Objective. Interleukin-1 (IL-1) and transforming growth factor ␤1 (TGF␤1) play major roles in osteoarticular diseases, exerting opposite effects on both the catabolism and anabolism of cartilage matrix. Previous findings suggest that IL-1 and TGF␤1 could function in a feedback interaction. However, the effect exerted by IL-1 on expression of TGF␤ by articular chondrocytes is, so far, poorly understood. The present study was carried out to determine the influence of IL-1␤ on the expression of TGF␤1 by bovine articular chondrocytes (BACs) in primary culture.Methods. BAC primary cultures were treated with IL-1␤, and TGF␤1 messenger RNA (mRNA) steadystate levels and protein expression were measured by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Transient transfection of TGF␤1 gene promoter constructs was performed to delineate the DNA sequences that mediate the IL-1␤ effect. Electrophoretic mobility shift assays (EMSAs) and supershift analysis were used to characterize the transcription factors binding to these sequences. Results. Cultured BACs responded to IL-1␤ ex-

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Osteoarthritic Human Cartilage Is More Sensitive to Transforming Growth Factor Than Is Normal Cartilage

Cited by 59 publications

References 0 publications

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Dynamic expression of transforming growth factor-betas (TGF-β) and their type I and type II receptors in the synovial tissue of arthritic rats

Mediation of interleukin‐1β–induced transforming growth factor β1 expression by activator protein 4 transcription factor in primary cultures of bovine articular chondrocytes: Possible cooperation with activator protein 1

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