Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. Influence of nitric oxide.

Amin, Ashok R.; Attur, Mukundan; Patel, Rajesh N.; Thakker, Geeta D.; Marshall, Paul; Rediske, John; Stuchin, Steven A.; Patel, Indravadan R.; Abramson, Steven B.

doi:10.1172/jci119280

Cited by 356 publications

(308 citation statements)

References 34 publications

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“…One of the genes that is upregulated in the inflammation process and has been implicated in osteoarthritis and colon cancer is the COX-2 enzyme. [36][37][38] Studies from our laboratory and others have shown that COX-2 activity increases dramatically in colon cancer tissues. 39 Since COX-2 is upregulated both in osteoarthritis and colon cancer, SAM seems to have a positive beneficial effect on both of these chronic diseases.…”

Section: Discussionmentioning

confidence: 98%

S‐adenosyl L‐methionine inhibits azoxymethane‐induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco‐2 cell growth in 3D culture

Guruswamy

Swamy

Choi

et al. 2007

Intl Journal of Cancer

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S-Adenosyl L-methionine (SAM) is a universal methyl group donor to various intermediary metabolites, hormones, proteins, neurotransmitters, phospholipids and nucleic acids. Deficiency of folate, which plays a role in the synthesis of SAM leads to increased risk for colon cancer. This study tested the effectiveness of SAM supplementation in protecting against azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. We also tested the effect of SAM on cyclooxygenase-2 (COX-2) in a macrophage cell line. Further, we developed a 3-D culture model using Caco-2 cells to test the effect of SAM on tumor spheroid size and number. Groups of rats were given the experimental diet containing either 0-, 400-or 800-ppm SAM, 1 week before the first AOM injection and continued until 8 weeks. In the control group, AOM produced a substantial number of aberrant crypt foci (ACF) (96 6 8). Dietary administration of SAM significantly reduced the number of total ACF (400 ppm SAM, 68 6 7.3, p < 0.01 and 800 ppm SAM, 57 6 7.1, p < 0.001). SAM significantly decreased AOM-induced colonic multicrypt foci in a dose-dependent manner. Suppression of Lipopolysaccharide (LPS) induced COX-2 protein expression was observed in a RAW264.7 cell line. We established growth of Caco-2 cells as spheroids, in a 3D matrix of collagen and matrigel. Treatment with SAM decreased both size and number of spheroids in a dose-dependent manner (p < 0.0001). These observations demonstrate for the first time that SAM can reduce the occurrence of ACF in AOM treated male F344 rats and suppress formation of human tumor spheroids and expression of COX-2. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 98%

S‐adenosyl L‐methionine inhibits azoxymethane‐induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco‐2 cell growth in 3D culture

Guruswamy

Swamy

Choi

et al. 2007

Intl Journal of Cancer

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“…Isolation of Bovine and Human Chondrocytes-Bovine cartilage was obtained from young calves, and chondrocytes were isolated from hooves by standard methods with minor modifications (11,12). The released cells were suspended in RPMI 1640 ϩ 10% FBS ϩ antibiotics and plated in a 24-well plate (Becton Dickinson, Lincoln Park, NJ) at a density of 5 ϫ 10 5 cells/2.0 cm 2 for 48 h. Human chondrocytes were isolated from OA-affected cartilage.…”

Section: Methodsmentioning

confidence: 99%

“…Organ Culture of OA Cartilage and Analysis of Mediators-Organ culture was carried out as described previously (11,13). Briefly, knee articular cartilage from patients undergoing knee replacement surgery was obtained and cut in 3-mm discs, and four to six discs (ϳ100 mg) were placed in organ culture in 2 ml of Ham's F-12 medium ϩ 0.1% human albumin for 24 -72 h, with or without modulators.…”

Section: Methodsmentioning

confidence: 99%

“…Isolation of RNA from Cells and OA Cartilage-The method was basically as described by Adams et al (16) with minor modifications (11). Briefly, the cartilage was milled into fine powder in liquid nitrogen and was extracted with 4 M guanidium thiocyanate, 25 mM sodium citrate, 0.5% sodium dodecyl sarcosine, and 0.1 M 2-mercaptoethanol for 4 h on a rocker.…”

Section: Methodsmentioning

confidence: 99%

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Reversal of Autocrine and Paracrine Effects of Interleukin 1 (IL-1) in Human Arthritis by Type II IL-1 Decoy Receptor

Attur¹,

Dave²,

Cipolletta³

et al. 2000

Journal of Biological Chemistry

119

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Interleukin 1 (IL-1), produced by both synovial cells and chondrocytes, plays a pivotal role in the pathogenesis of cartilage destruction in osteoarthritis (OA). We examined the specific expression and function of IL-1 receptor family-related genes in human joint tissues. Gene array analysis of human normal and OA-affected cartilage showed mRNA expression of IL-1 receptor accessory protein (IL-1RAcp) and IL-1 type I receptor (IL-1RI), but not IL-1 antagonist (IL-1ra) and IL-1 type II decoy receptor (IL-1RII). Similarly, human synovial and epithelial cells showed an absence of IL-1RII mRNA. Functional genomic analyses showed that soluble (s) IL-1RII, at picomolar concentrations, but not soluble TNF receptor:Fc, significantly inhibited IL-1␤-induced nitric oxide (NO) and/or prostaglandin E 2 production in chondrocytes, synovial and epithelial cells. In OA-affected cartilage, the IC 50 for inhibition of NO production by sIL-1RII was 2 log orders lower than that for sIL-1RI. Human chondrocytes that overexpressed IL-1RII were resistant to IL-1-induced IL-1␤ mRNA accumulation and inhibition of proteoglycan synthesis. In osteoarthritis, deficient expression by chondrocytes of innate regulators or antagonists of IL-1 such as IL-1ra and IL-1RII (soluble or membrane form) may allow the catabolic effects of IL-1 to proceed unopposed. The sensitivity of IL-1 action to inhibition by sIL-1RII has therapeutic implications that could be directed toward correcting this unfavorable tissue(s) dependent imbalance. Osteoarthritis (OA)1 is considered a non-inflammatory arthritis, characterized by a limited infiltration of neutrophils into the synovial space and, in general, an absence of the classical signs of inflammation. Chondrocytes embedded within articular cartilage that is avascular and aneural reside in a sequestered environment, perhaps more than other cell types, whereby cellular metabolism is regulated by an autocrine mechanism responsive to biomechanical and pericellular signals. Recent observations by this and other laboratories indicate that, despite the general absence of clinical signs of inflammation, chondrocytes derived from patients with OA, show superinduction of proinflammatory genes typically associated with the products of synovial tissues in rheumatoid arthritis, including nitric-oxide synthase, cyclooxygenase-2, TNF␣, IL-6, and IL-8. The spontaneous production of the corresponding gene products and inflammatory mediators promotes a catabolic state, which leads to progressive cartilage damage in OA (1-4). This intraarticular inflammatory response in OA-affected cartilage, which may be considered as an in situ "molecular inflammation," is partially dependent on autocrine IL-1␤ production, which induces and sustains an imbalance of cartilage homeostasis and extracellular matrix synthesis (5). The autocrine production of IL-1 in OA-affected cartilage is amplified by engagement of integrins such as ␣ 5 ␤ 1 by abnormally expressed extracellular matrix proteins, including proteolytic fragments of fibronectin (5, 6)...

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“…IL-1b and PGE 2 concentration are markedly elevated in the synovial fluid of patients with rheumatoid arthritis (RA) (3) and osteoarthritis (OA) (4)(5)(6). Chondrocytes from human OA cartilage explants spontaneously produce PGE 2 (7).…”

mentioning

confidence: 99%

Inhibition of Matrix Metalloproteinase-3 and -13 Synthesis Induced by IL-1β in Chondrocytes from Mice Lacking Microsomal Prostaglandin E Synthase-1

Gosset

Pigenet

Salvat

et al. 2010

The Journal of Immunology

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Joint destruction in arthritis is in part due to the induction of matrix metalloproteinase (MMP) expression and their inhibitors, especially MMP-13 and -3, which directly degrade the cartilage matrix. Although IL-1β is considered as the main catabolic factor involved in MMP-13 and -3 expression, the role of PGE2 remains controversial. The goal of this study was to determine the role of PGE2 on MMP synthesis in articular chondrocytes using mice lacking microsomal PGE synthase-1 (mPGES-1), which catalyses the rate-limiting step of PGE2 synthesis. MMP-3 and MMP-13 mRNA and protein expressions were assessed by real-time RT-PCR, immunoblotting, and ELISA in primary cultures of articular chondrocytes from mice with genetic deletion of mPGES-1. IL-1β–induced PGE2 synthesis was dramatically reduced in mPGES-1−/− and mPGES-1+/− compared with mPGES-1+/+ chondrocytes. A total of 10 ng/ml IL-1β increased MMP-3 and MMP-13 mRNA, protein expression, and release in mPGES-1+/+ chondrocytes in a time-dependent manner. IL-1β–induced MMP-3 and MMP-13 mRNA expression, protein expression, and release decreased in mPGES-1−/− and mPGES-1+/− chondrocytes compared with mPGES-1+/+ chondrocytes from 8 up to 24 h. Otherwise, MMP inhibition was partially reversed by addition of 10 ng/ml PGE2 in mPGES-1−/− chondrocytes. Finally, in mPGES-1−/− chondrocytes treated by forskolin, MMP-3 protein expression was significantly decreased compared with wild-type, suggesting that PGE2 regulates MMP-3 expression via a signaling pathway dependent on cAMP. These results demonstrate that PGE2 plays a key role in the induction of MMP-3 and MMP-13 in an inflammatory context. Therefore, mPGES-1 could be considered as a critical target to counteract cartilage degradation in arthritis.

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Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. Influence of nitric oxide.

Cited by 356 publications

References 34 publications

S‐adenosyl L‐methionine inhibits azoxymethane‐induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco‐2 cell growth in 3D culture

S‐adenosyl L‐methionine inhibits azoxymethane‐induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco‐2 cell growth in 3D culture

Reversal of Autocrine and Paracrine Effects of Interleukin 1 (IL-1) in Human Arthritis by Type II IL-1 Decoy Receptor

Inhibition of Matrix Metalloproteinase-3 and -13 Synthesis Induced by IL-1β in Chondrocytes from Mice Lacking Microsomal Prostaglandin E Synthase-1

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