Generation of kinins in synovial fluid from patients with arthropathy

Bond, A.; Lemon, Marius; Dieppe, Paul; Bhoola, K. D.

doi:10.1016/s0162-3109(97)00023-4

Cited by 23 publications

(14 citation statements)

References 18 publications

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“…We identified two elements of this system, namely kininogen-1 and N-carboxypeptidase, which is a zinc metalloprotease that degrades bradykinin and anaphylactic peptides of the complement system [65]. These observations are congruent with previous work showing that SF contains all of the components needed to generate kinins [66]. It is possible that disequilibrium between the rate of formation and breakdown of kinins results in the inflammation, joint pain, and swelling that are seen in patients with arthritis.…”

Section: Discussionsupporting

confidence: 82%

High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis

et al. 2007

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The development of increasingly high-throughput and sensitive mass spectroscopy-based proteomic techniques provides new opportunities to examine the physiology and pathophysiology of many biologic fluids and tissues. The purpose of this study was to determine protein expression profiles of high-abundance synovial fluid (SF) proteins in health and in the prevalent joint disease osteoarthritis (OA). A cross-sectional study of 62 patients with early OA (n = 21), patients with late OA (n = 21), and control individuals (n = 20) was conducted. SF proteins were separated by using one-dimensional PAGE, and the in-gel digested proteins were analyzed by electrospray ionization tandem mass spectrometry. A total of 362 spots were examined and 135 high-abundance SF proteins were identified as being expressed across all three study cohorts. A total of 135 SF proteins were identified. Eighteen proteins were found to be significantly differentially expressed between control individuals and OA patients. Two subsets of OA that are not dependent on disease duration were identified using unsupervised analysis of the data. Several novel SF proteins were also identified. Our analyses demonstrate no disease duration-dependent differences in abundant protein composition of SF in OA, and we clearly identified two previously unappreciated yet distinct subsets of protein profiles in this disease cohort. Additionally, our findings reveal novel abundant protein species in healthy SF whose functional contribution to SF physiology was not previously recognized. Finally, our studies identify candidate biomarkers for OA with potential for use as highly sensitive and specific tests for diagnostic purposes or for evaluating therapeutic response.

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Section: Discussionsupporting

confidence: 82%

High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis

et al. 2007

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“…The presence of BK has been found also in the synovial fluid of patients affected by rheumatoid arthritis, and the B 2 receptors have been demonstrated on synovial lining cells, fibroblasts, and endothelial cells of blood vessels from patients affected by OA (Bond et al, 1997;Cassim et al, 1997). Moreover, BK involvement in OA pain, through B 2 receptors, has been shown in patients with symptomatic knee osteoarthritis in which intra-articular injection of the B 2 receptor antagonist icatibant reduced pain intensity (Sorbera et al, 2006;Song et al, 2009).…”

mentioning

confidence: 98%

Effect of Intra-articular 4-(S)-Amino-5-(4-{4-[2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl} piperazino)-5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132), a Kinin B₂ Receptor Antagonist, on Nociceptive Response in Monosodium Iodoacetate-Induced Experimental Osteoarthritis in Rats

Cialdai

Giuliani²,

Valenti³

et al. 2009

J Pharmacol Exp Ther

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The present study was designed to investigate the role of bradykinin (BK) in the knee joint osteoarthritis induced by intraarticular (i.ar.) administration of monosodium iodoacetate (MIA) in the rat, and to determine the efficacy of the kinin B 2 receptor antagonists, 4-(S)-amino-5-(4-{4-[2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl} piperazino)-5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132) and icatibant, in reducing pain. Rats received MIA (1 mg/25 l i.ar.) in the right knee. MEN16132, icatibant (1, 3, and 10 g/25 l i.ar.), or saline were administered 7 days after MIA treatment, and their antinociceptive effect was observed for 2 weeks. MEN16132 induced a marked and sustained reduction of incapacitation produced by MIA, approximately 56% inhibition of pain at 3 g/knee. MEN16132 analgesia was more potent and longer lasting, up to 10 days, than icatibant. MEN16132 (3 g/knee), at different time points from MIA treatment in separate groups of animals, produced comparable maximal antinociceptive effects, whereas the pain response induced by MIA was unaffected if MEN16132 (10 g/knee) was administered in the contralateral knee. Indomethacin at high doses (100 -625 g/knee) inhibited by approximately 40% but with a short duration the MIAinduced pain. MIA treatment produced a significant increase of BK and prostaglandin E 2 (PGE 2 ) metabolite levels in synovial fluid up to 21 days, and PGE 2 metabolite levels were reduced almost to basal values by MEN16132. In conclusion the potent and long-lasting analgesic effect of MEN16132 in MIA-induced osteoarthritis indicates an important role for BK in osteoarthritic pain, and suggests that MEN16132 can be a candidate for the treatment of this chronic disease.Osteoarthritis (OA) is a degenerative joint disease that affects most of the elderly population causing chronic pain and joint disability. In particular, the OA of the knee is characterized by histological changes of the joint involving degeneration of articular cartilage with fibrillation and erosion, synovitis, remodeling of subchondral bone with osteophytes formation at the joint margins, and sclerosis of subchondral bone (Goldring and Goldring, 2007). The pathophysiology behind these modifications is complex and involves a combination of mechanical, cellular, and biochemical processes that are not yet completely understood. Inflammation contributes to increase structural degeneration by releasing catabolic and proinflammatory mediators including cytokines, nitric oxide, and matrix metalloproteinases that may activate chondrocytes and synovial fibroblasts leading to cartilage destruction (Goldenberg et al., 1982;Yasuda, 2006;Sutton et al., 2009). No drug modifying OA progression is currently available, and treatment options are focused on symptomatic relief of pain and inflammation to improve the joint function. Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and opiates are widely used, but Article, publication date, and c...

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“…Initially evidence of the presence of BK in the synovial fluid from patients affected by arthritis of different etiologies, including OA, was early presented [28,29] and later confirmed [30][31][32]. The synovial BK content ranged between 1 to 60 nM, thus in concentrations that were able to produce responses in isolated synovial cells (Table 3).…”

Section: Bk and B 2 Receptors In The Synovial Fluid And Synovium Of Omentioning

confidence: 98%

Knee osteoarthritis: a role for bradykinin?

Meini

Maggi

2008

Inflamm. res.

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Osteoarthritis (OA) is a painful and degenerating progressive disease of the joints which affects millions of patients worldwide. The cause of OA is largely unknown. Among the potential therapies for the symptomatic treatment of OA, the intra-articular administration of a specific bradykinin (BK) B2 receptor antagonist has been reported to produce a long lasting analgesic effect in patients affected by knee OA. BK is a vasodilator and inflammatory nonapeptide which is generated in OA synovium. It contributes to the initiation and maintenance of inflammation, to exciting and sensitizing sensory nerve fibres, thus producing pain, and to activating synoviocytes and chondrocytes which are the main cells involved in the homeostasis of synovial fluid and cartilage, respectively. Moreover, BK synergistically potentiates the effects produced by pro-inflammatory cytokines. Biochemical and preclinical evidence supporting the therapeutic relevance of B2 receptor blockade in OA pathophysiology are reviewed in this publication.

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Generation of kinins in synovial fluid from patients with arthropathy

Cited by 23 publications

References 18 publications

High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis

High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis

Knee osteoarthritis: a role for bradykinin?

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