Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitrostudy

Andreas, Kristin; Lübke, Carsten; Häupl, Thomas; Dehne, Tilo; Morawietz, Lars; Ringe, Jochen; Kaps, Christian; Sittinger, Michael

doi:10.1186/ar2358

Cited by 104 publications

(103 citation statements)

References 60 publications

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“…Whereas murine CIA membranes also contain T cell populations and monocyte-macrophage-like cells (41), the proportion of fibroblast-like cells is thought to be higher in murine CIA membrane preparations. Because these cells are potent producers of IL-6 (42,43), this finding may offer an explanation for the enhanced role of IL-6 and, thus, the effectiveness of PGE 2 inhibition in CIA.…”

Section: Discussionmentioning

confidence: 99%

Nonsteroidal Anti-Inflammatory Drugs Increase TNF Production in Rheumatoid Synovial Membrane Cultures and Whole Blood

Page

Turner

Brown

et al. 2010

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

Nonsteroidal Anti-Inflammatory Drugs Increase TNF Production in Rheumatoid Synovial Membrane Cultures and Whole Blood

Page

Turner

Brown

et al. 2010

The Journal of Immunology

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“…Transgenic mice expressing TNF-α, a model of polyarthritis (5), display chondrocyte apoptosis before the onset of full arthritis, suggesting that cytokine-induced chondrocyte apoptosis is a primary cause of, rather than an event secondary to, cartilage matrix breakdown (6). Thus, factors able to counteract chondrocyte apoptosis under inflammatory conditions are relevant for the treatment of RA (7)(8)(9)(10)(11). One such factor is prolactin (PRL).…”

Section: Introductionmentioning

confidence: 99%

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

et al. 2013

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Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3-dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor-null (Prlr -/-) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA.

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“…2,3) Recently, genetic and environmental factors have been found to be associated with the etiology or pathogenesis of RA. 4,5) In the treatment of RA, pharmacotherapy is very important.…”

mentioning

confidence: 99%

Chondroitin Sulfate–Glycyl-Prednisolone Conjugate as Arthritis Targeting System: Localization and Drug Release in Inflammatory Joints

Onishi

Yoshida

Matsuyama

2014

Biological & Pharmaceutical Bulletin

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Chondroitin sulfate-glycyl-prednisolone conjugate (CS-GP) was previously demonstrated to exhibit superior anti-arthritic effects compared to prednisolone (PD) alone. In this study, CS-GP was examined for its pharmacokinetic features and tropism for inflammatory joints using rats with adjuvant-induced arthritis in order to identify the mechanism of the potential enhancement. After intravenous injection (2.5 mg PD eq./ kg), CS-GP yielded an area under the curve (AUC) of the total (free conjugated) drug much higher than that of PD alone. After intravenous administration at the same dose, the drug distribution to the hind paw inflammatory joints was investigated. For PD alone, the PD concentration was 1.2-1.7 µg/g at 1 h and fell to 0.12-0.14 µg/g at 24 h. In contrast, CS-GP maintained the total concentration in the range of 0.55-0.97 µg/g for 1-24 h, and maintained the free PD concentration at 0.06-0.16 µg/g for 1-24 h. Furthermore, at 24 h after intravenous administration (2.5 mg PD eq./kg), CS-GP exhibited a higher total drug concentration in arthritic rats than in healthy rats. These findings suggested that CS-GP may have the ability to target inflammatory joints. As the apparent molecular weight of CS-GP became greater in plasma, it might interact with blood components and cause high plasma retention and good tropism to the inflammatory sites. Enhancement of the anti-inflammatory potential of CS-GP was found to be due to good maintenance of drug levels in the inflamed area.

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Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitrostudy

Cited by 104 publications

References 60 publications

Nonsteroidal Anti-Inflammatory Drugs Increase TNF Production in Rheumatoid Synovial Membrane Cultures and Whole Blood

Nonsteroidal Anti-Inflammatory Drugs Increase TNF Production in Rheumatoid Synovial Membrane Cultures and Whole Blood

Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

Chondroitin Sulfate–Glycyl-Prednisolone Conjugate as Arthritis Targeting System: Localization and Drug Release in Inflammatory Joints

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