In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-beta 1: age-related differences.

Beuningen, H.M. van; Kraan, P.M. van der; Arntz, Onno J.; Berg, Wim B. van den

doi:10.1136/ard.53.9.593

Cited by 87 publications

(60 citation statements)

References 48 publications

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“…The expression of TGF-1 and TGF-2 at the cartilage-pannus junction indicates that these TGF-s may be involved in tissue repair. It is known that TGF-1 counteracts the effects of proinflammatory cytokines such as IL-1 and tumour necrosis factor-alpha (TNF-) [20]. Nevertheless, high production of IL-1 and TNF-is documented to occur in arthritic joints [21,22].…”

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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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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“…Each specimen was dissolved in 0.5 ml Soluene overnight at 3120 DUMOND ET AL 42°C. The 35 S content was measured by liquid scintillation counting.…”

Section: Methodsmentioning

confidence: 99%

“…In response to cartilage damage, various growth factors, including insulin-like growth factor 1 (IGF-1) or transforming growth factor ␤ (TGF␤), are activated and stimulate chondrocytes to repair the damaged extracellular matrix by forming cell clusters and increasing their anabolic activity (30)(31)(32)(33). In fact, TGF␤ has a dual role in OA, having a beneficial effect on cartilage repair but inducing osteophyte formation (34,35). Despite the increased synthetic response induced by growth factors, the enhanced synthesis of degrading enzymes ultimately results in cartilage erosion.…”

Section: Conclusion These Findings Suggest a New Peripheral Functionmentioning

confidence: 99%

“…B, Proteoglycan synthesis in cartilage specimens was measured by Na 2 35 SO 4 incorporation, 48 hours following intraarticular injection of 10, 30, 100, or 300 g of rat recombinant leptin. Results (mean and SEM) are expressed as the percentage of 35 S incorporation in leptininjected rats compared with that in saline-injected rats, and represent 1 of 3 experiments (n ϭ 6 per group). ‫ء‬ ϭ P Ͻ 0.05; ‫ءء‬ ϭ P Ͻ 0.01.…”

mentioning

confidence: 99%

“…We investigated the effects of leptin on proteoglycan anabolism by measuring 35 S incorporation in 4 areas of the tibial plateaus (medial and lateral) after intraarticular injection of leptin (10, 30, 100, and 300 g/50 l) into the right knee joint ( Figure 5A). After a 30-g injection, a marked increase in proteoglycan synthesis was observed in all cartilage areas of the plateau ( Figure 5B).…”

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confidence: 99%

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Evidence for a key role of leptin in osteoarthritis

Dumond¹,

Presle²,

Terlain³

et al. 2003

Arthritis & Rheumatism

495

416

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Objective. To evaluate the contribution of leptin (an adipose tissue-derived hormone) to the pathophysiology of osteoarthritis (OA), by determining the level of leptin in both synovial fluid (SF) and cartilage specimens obtained from human joints. We also investigated the effect of leptin on cartilage, using intraarticular injections of leptin in rats.Methods. Leptin levels in SF samples obtained from OA patients undergoing either knee replacement surgery or knee arthroscopy were measured by enzymelinked immunosorbent assay. In addition, histologic sections of articular cartilage and osteophytes obtained during surgery for total knee replacement were graded using the Mankin score, and were immunostained using antibodies to leptin, transforming growth factor ␤ (TGF␤), and insulin-like growth factor 1 (IGF-1). For experimental studies, various doses of leptin (10, 30, 100, and 300 g) were injected into the knee joints of rats. Tibial plateaus were collected and processed for proteoglycan synthesis by radiolabeled sulfate incorporation, and for expression of leptin, its receptor (ObRb), and growth factors by reverse transcriptasepolymerase chain reaction and immunohistochemical analysis.Results. Leptin was observed in SF obtained from human OA-affected joints, and leptin concentrations correlated with the body mass index. Marked expression of the protein was observed in OA cartilage and in osteophytes, while in normal cartilage, few chondrocytes produced leptin. Furthermore, the pattern and level of leptin expression were related to the grade of cartilage destruction and paralleled those of growth factors (IGF-1 and TGF␤1). Animal studies showed that leptin strongly stimulated anabolic functions of chondrocytes and induced the synthesis of IGF-1 and TGF␤1 in cartilage at both the messenger RNA and the protein levels.Conclusion. These findings suggest a new peripheral function of leptin as a key regulator of chondrocyte metabolism, and indicate that leptin may play an important role in the pathophysiology of OA.

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