Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2

Brooks, Peter; Emery, Paul; Evans, Jilly F.; Fenner, Helmut; Hawkey, Chris J.; Patrono, Carlo; Smolen, Josef S; Breedveld, Ferdinand C.; Day, Richard O.; Dougados, Maxime; Ehrich, Elliot W.; Gijón-Baños, J; Kvien, Tore K; Rijswijk, M.H. van; Warner, Timothy D.; Zeidler, Henning

doi:10.1093/rheumatology/38.8.779

Cited by 200 publications

(126 citation statements)

References 70 publications

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“…IM is a potent inhibitor of cyclooxygenase, both constitutive COX-1 and inducible COX-2 isoforms, which are responsible for prostanoids synthesis in tissues (Vane et al, 1998). It is assumed that whereas inhibition of COX-2 leads to supression of inflammation, drug inhibition of COX-1 is responsible for functional and structural alterations in the gastro-intestinal mucosa, if drug is ingested (Brooks et al, 1999). Nevertheless, this cyclooxygenase inhibition does not fully explain pathogenesis of the drug-induced enteropathy.…”

Section: Discussionmentioning

confidence: 99%

Assessment of intestinal permeability in preruminant calves by lactulose/mannitol test

Klein¹,

Moravcová²,

Kleinová³

et al. 2007

J. Anim. Feed Sci.

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The aim of this study was to utilize the lactulose/mannitol test for assessment of intestinal permeability (IP) in preruminant calves. IP was increased experimentally by administration of Indomethacin. Both sugar markers were determined simultaneously as silyl-derivates in 5 h urinary production using the gas liquid chromatography technique. The index of IP was determined as the ratio between urinary recovery (%) of 10 g lactulose to 5 g D-mannitol. The IP index in control calves was 0.242±0.048. Doses of 20 and 60 mg Indomethacin did not significantly affect IP, but the IP index was significantly enhanced in calves receiving 120 mg of drug (0.541±0.091; P<0.01). Results of this study show that ratio of lactulose to D-mannitol in urine reflected the treatment by the highest dose of Indomethacin and that the test may be used for determination of IP in preruminant calves.

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Section: Discussionmentioning

confidence: 99%

Assessment of intestinal permeability in preruminant calves by lactulose/mannitol test

Klein¹,

Moravcová²,

Kleinová³

et al. 2007

J. Anim. Feed Sci.

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“…COX-2 selective inhibition has the potential value of reducing gastrointestinal system side effects, 9 while selectively inhibiting the inducible COX enzyme. 30 Early studies documented that the COX-2 expression was detected in synovial membrane biopsy samples from RA patients, but not in normal synovium. 28 Subacromial bursal tissue has a synovial microenvironment which shares very similar histologic features and cell types with RA synovium.…”

Section: Discussionmentioning

confidence: 99%

Stromal cell‐derived factor 1 (SDF‐1, CXCL12) is increased in subacromial bursitis and downregulated by steroid and nonsteroidal anti‐inflammatory agents

Kim

Bigliani

Fujisawa

et al. 2006

Journal Orthopaedic Research

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Several studies have demonstrated that inflammation in the subacromial bursa is an important component in the pathogenesis of impingement syndrome. We have demonstrated in a previous study that many inflammatory cytokines, including stromal cell-derived factor 1 (SDF-1, CXCL12), are increased in the subacromial bursa [Blaine et al. 2005. J Shoulder Elbow Surg 14(Suppl 1):84S-89S]. SDF-1 is a potent chemotactic and angiogenic factor that stimulates recruitment of inflammatory cells. In the current study, we proposed that the resident cells in subacromial bursal tissue produce SDF-1, which can play a role in the inflammatory reponse of bursal tissue, and that this chemokine can be regulated by steroid (dexamethasone) and nonsteroidal anti-inflammatory medications (NSAIDs).Twenty-two subacromial bursa tissues (18 bursitis and 4 normal bursa) were obtained intraoperatively from patients during shoulder surgery and analyzed using the cDNA Array technique in accordance with an IRB approved protocol. cDNA array results were confirmed with real-time reverse transcription-polymerase chain reaction (RT-PCR). Bursal cells (from 4 normal bursa, 3 bursitis) and two normal bone marrow with whole tissue explants were cultured for one passage. Cell culture supernatants were collected and SDF-1 protein was detected with enzyme-linked immunosorbent assay (ELISA). Cultured bursal cells were treated with a COX-2 inhibitor and dexamethasone, and cells was harvested at 1-day and 4-day intervals. SDF-1 expression was evaluated by real-time RT-PCR and ELISA. cDNA Array analysis demonstrated that the gene expression of SDF-1 was increased in patients with subacromial bursitis compared to controls ( p < 0.05). Real-time RT-PCR also revealed that the mRNA expression of SDF-1 in bursitis tissue is increased 10-fold over control tissue. While the normal bursal cells produced negligible amounts of SDF-1 protein, cultured cells derived from bursitis lesion released as much SDF-1 protein (235 pg/100,000 cells) as normal bone marrow stromal cells (283 pg/ 100,000 cells) as measured by ELISA. The addition of a COX-2 inhibitor and dexamethasone to bursitis cell lines led to decreased SDF-1 expression levels compared to untreated bursitis cell lines. These studies demonstrate that there is a significant elevation of SDF-1 expression in the subacromial bursa of patients with rotator cuff disease. Furthermore, this chemokine can be downregulated by COX-2 inhibitors and steroids. These results provide biologic evidence for the use of steroid and NSAIDs in the treatment of subacromial bursitis. In the future, targeted inhibition of molecules such as SDF-1 in the subacromial bursa may present a therapeutic strategy that may avoid the side effects of these other (steroid and NSAID) medications. ß

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“…Non steroidal anti-inflammatory drugs (NSAIDs) are widely used systemic inhibitors of infl ammatory prostaglandin production by cyclooxygenases (COX-1 and COX-2) (Brooks et al, 1999). In orthopaedic surgery the use of NSAIDs is under debate, as systemic NSAID treatment delays spinal fusion in patients and animal models (Thaller et al, 2005) and fracture healing of the long bones (Goodman et al, 2002;Gerstenfeld et al, 2003;Simon and O'Connor, 2007;Herbenick et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification

Welting

Caron²,

Emans

et al. 2011

eCM

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Skeletogenesis and bone fracture healing involve endochondral ossification, a process during which cartilaginous primordia are gradually replaced by bone tissue. In line with a role for cyclooxygenase-2 (COX-2) in the endochondral ossifi cation process, non-steroidal anti-inflammatory drugs (NSAIDs) were reported to negatively affect bone fracture healing due to impaired osteogenesis. However, a role for COX-2 activity in the chondrogenic phase of endochondral ossifi cation has not been addressed before. We show that COX-2 activity fulfi ls an important regulatory function in chondrocyte hypertrophic differentiation. Our data reveal essential cross-talk between COX-2 and bone morphogenic protein-2 (BMP-2) during chondrocyte hypertrophic differentiation. BMP-2 mediated chondrocyte hypertrophy is associated with increased COX-2 expression and pharmacological inhibition of COX-2 activity by NSAIDs (e.g., Celecoxib) decreases hypertrophic differentiation in various chondrogenic models in vitro and in vivo, while leaving early chondrogenic development unaltered. Our fi ndings demonstrate that COX-2 activity is a novel factor partaking in chondrocyte hypertrophy in the context of endochondral ossifi cation and these observations provide a novel etiological perspective on the adverse effects of NSAIDs on bone fracture healing and have important implications for the use of NSAIDs during endochondral skeletal development.

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Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2

Cited by 200 publications

References 70 publications

Assessment of intestinal permeability in preruminant calves by lactulose/mannitol test

Assessment of intestinal permeability in preruminant calves by lactulose/mannitol test

Stromal cell‐derived factor 1 (SDF‐1, CXCL12) is increased in subacromial bursitis and downregulated by steroid and nonsteroidal anti‐inflammatory agents

Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification

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