In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage

Ratcliffee, Anthony; Azzo, Walid; Saed‐Nejad, Fatemeh; Lane, Nancy E.; Rosenwasser, Melvin P.; Mow, Van C.

doi:10.1002/jor.1100110203

Cited by 22 publications

(17 citation statements)

References 52 publications

(71 reference statements)

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“…At least 4 other drugs that inhibit prostaglandin synthesis have been examined in the OA dog model. Tiaprofenic acid (36) and diclofenac (this study) showed modest activity, naproxen may affect some biochemical parameters (37), and aspirin accel-erated the development of severe OA (38). Thus, we think it unlikely that the effects of tenidap reported herein are simply due its inhibitory activity on prostaglandin synthesis.…”

Section: Discussionmentioning

confidence: 90%

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Fernandes

Martel‐Pelletier

Otterness

et al. 1995

Arthritis & Rheumatism

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Objective. To examine the effects of tenidap and diclofenac on osteoarthritic lesions and metalloprotease activity in experimental osteoarthritis (OA).Methods. The anterior cruciate ligament of the right stifle joint of 25 mongrel dogs was sectioned by a stab wound. Seven dogs received no treatment, 6 were treated with oral omeprazole (20 mg/day), another 6 were treated with diclofenac (0.25 mg/kg/twice daily) plus omeprazole (20 mg/day), and 6 received oral tenidap (3 mg/kg/twice daily) plus omeprazole (20 mg/ day). The dogs received medication for 8 weeks; all dogs were killed at the end of this period. Eight normal dogs were used as controls. Lesions were evaluated macroscopically for the incidence and size of osteophytes and the area and grade of cartilage erosions on the condyles and plateaus, along with histologic evaluation of the severity of the cartilage lesions and synovial inflammation. Stromelysin and collagenase activities and the collagenase messenger RNA (mRNA) level were measured in cartilage and synovial membrane.Results. Compared with the untreated or omeprazole-treated OA groups, the dogs treated with tenidap exhibited significant reduction in the incidence (P 5 0.001) and size (P 5 0.0001) of osteophytes. Tenidap also significantly decreased the size and grade of cartilage macroscopic lesions, as well as the histologic severity of cartilage lesions on both condyles and plateaus. The histologic severity of synovial inflammatory reaction was also significantly reduced (P I 0.003) in the tenidap group. Tenidap markedly decreased stromelysin and collagenase activity in both cartilage (stromelysin P I 0.003; collagenase P I 0.01) and synovial membrane (stromelysin P 5 0.003; collagenase P 5 0.005). Moreover, tenidap also decreased the collagenase mRNA level in cartilage (P 5 0.005) and synovial membrane (P 5 0.002). Diclofenac slightly reduced the incidence and size of osteophytes and cartilage lesions, but these changes were not statistically significant. Diclofenac had no effect on the severity of synovial inflammation, metalloprotease activity, or collagenase expression.Conchsion. This study showed that tenidap had a more potent anti-osteoarthritic effect than diclofenac in this model. The effect of the drug in suppressing metalloprotease synthesis, a process known to play a major role in the pathophysiology of osteoarthritic lesions, may explain its mechanism of action.Transection of the anterior cruciate ligament of the dog knee leads to articular changes which resemble the morphologic and biochemical changes seen in human osteoarthritis (OA) (1-3). Cartilage lesions are probably related to mechanical as well as biochemical factors, including the enzymatic cleavage of matrix macromolecules (4). Matrix metalloproteases (MMP), such as collagenase and stromelysin, have been found to be significantly increased in OA cartilage and synovial membrane, in humans as well as in the experimental dog model (4-6). It is becoming more and more

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Section: Discussionmentioning

confidence: 90%

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Fernandes

Martel‐Pelletier

Otterness

et al. 1995

Arthritis & Rheumatism

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“…Recently, Pelletier et al reported that the NSAID, carprofen, reduced the structural changes and abnormal bone metabolism in an experimental dog OA model (51). In addition, some reports have shown positive effects of NSAIDs on cartilage integrity through suppression of proteoglycan degradation in vitro (52, 53) and in vivo (54, 55). In contrast, several reports indicate that these compounds do not have any positive effect on IL‐1β‐stimulated proteoglycan degradation (38, 53).…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase 2‐dependent prostaglandin E₂ modulates cartilage proteoglycan degradation in human osteoarthritis explants

Hardy¹,

Seibert²,

Manning³

et al. 2002

Arthritis & Rheumatism

289

210

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Objective To examine cyclooxygenase‐2 (COX‐2) enzyme expression, its regulation by interleukin‐1β (IL‐1β), and the role of prostaglandin E2 (PGE2) in proteoglycan degradation in human osteoarthritic (OA) cartilage. Methods Samples of human OA articular cartilage, meniscus, synovial membrane, and osteophytic fibrocartilage were obtained at knee arthroplasty and cultured ex vivo with or without IL‐1β and COX inhibitors. COX expression was evaluated by immunohistochemistry and Western blot analysis. The enzymatic activity of COX was measured by conversion of arachidonic acid to PGE2. Cartilage degradation was evaluated by measuring the accumulation of sulfated glycosaminoglycans in the medium. Results IL‐1β induced robust expression of COX‐2 and PGE2 in OA meniscus, synovial membrane, and osteophytic fibrocartilage explants, whereas low levels were produced in OA articular cartilage. IL‐1β also induced cartilage proteoglycan degradation in OA synovial membrane‐cartilage cocultures. Increased proteoglycan degradation corresponded to the induction of COX‐2 protein expression in, and PGE2 production from, the synovial membrane. Dexamethasone, neutralizing IL‐1β antibody, or the selective COX‐2 inhibitor, SC‐236, attenuated both the IL‐1β‐induced PGE2 production and cartilage proteoglycan degradation in these cocultures. The addition of PGE2 reversed the inhibition of proteoglycan degradation caused by SC‐236. Conclusion IL‐1β‐induced production of COX‐2 protein and PGE2 was low in OA articular cartilage compared with that in the other OA tissues examined. IL‐1β‐mediated degradation of cartilage proteoglycans in OA synovial membrane‐cartilage cocultures was blocked by the selective COX‐2 inhibitor, SC‐236, and the effect of SC‐236 was reversed by the addition of exogenous PGE2. Our data suggest that induction of synovial COX‐2‐produced PGE2 is one mechanism by which IL‐1β modulates cartilage proteoglycan degradation in OA.

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“…According to reports in the literature (Arumugham and Bose, 1981;Goodman et al, 2002;Muscará et al, 2000;Ratcliffe et al, 1993;Sadowski and Steinmeyer, 2001;Smith et al, 1995;Solheim et al, 1986;Srinivas et al, 1994), naproxen may affect, or not, the collagen synthesis in mammals depending on the dose applied. Böckelmann and Bechara (2004) and that failing, to alter the regeneration of the carp tail fin (10.4 mg.L -1 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is used in the treatment of osteoarthritis, rheumatoid arthritis, gout and rheumatism of soft tissue and is also indicated for periarticular and musculoskeletal diseases (Hanson et al, 2005;Mendias et al, 2004;Ratcliffe et al, 1993).…”

Section: Ultrastructural Processmentioning

confidence: 99%

“…However, there are controversial reports in the literature about the action of naproxen on the connective tissue, especially regarding collagen synthesis (Bjelle and Eronen, 1991;Goodman et al, 2002;Ratcliffe et al, 1993;Riley et al, 2001;Smith et al, 1995;Solheim et al, 1986;Srinivas et al, 1994). Muscará et al (2000) observed that naproxen decreased the deposition of collagen when administered in the healing of tissue wounds.…”

Section: Ultrastructural Processmentioning

confidence: 99%

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The regeneration of the tail fin actinotrichia of carp (Cyprinus carpio, Linnaeus, 1758) under the action of naproxen

Böckelmann

Bechara

2009

Braz. J. Biol.

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A conglomerate of small, rigid, fusiform spicules known as actinotrichia sustains the edge of tail fins of teleost. After amputation, these structures show an extremely fast regenerative capacity. In this study we observed the effect of a nonsteroidal anti-inflammatory drug, naproxen, used in the treatment of degenerative articular diseases, during the process of actinotrichia regeneration. For this purpose, regenerating tissue from animals in contact with the drug was submitted to histochemical and ultrastructural analysis in comparison to tissue from animals under normal conditions, i.e., not in contact with the drug in question. Actinotrichia regeneration was similar in both animals, indicating that naproxen, at the dose used in the present study, did not interfere with actinotrichia synthesis during the regenerative process of the tail fin. This could be because naproxen did not influence the expression of the genes required for the regeneration process, such as the Sonic hedgehog (Shh) gene, which is involved in actinotrichia formation.Keywords: caudal fin, tissue regeneration, elastoidin, nonsteroidal anti-inflammatory drug, fish.A regeneração das actinotriquias da nadadeira caudal da carpa (Cyprinus carpio, Linnaeus, 1758) sob a ação do naproxeno ResumoA borda da nadadeira caudal de teleósteo é sustentada por um conglomerado de espículas pequenas, rígidas e fusiformes chamadas actinotriquias. Essas estruturas, após a amputação, apresentam uma capacidade regenerativa extremamente rápida. Neste trabalho estudamos o efeito de uma droga anti-inflamatória não esteroide, o naproxeno, utilizada no tratamento de doenças articulares degenerativas, durante o processo de regeneração da actinotriquia. Para isso foram feitas análises histoquímicas e ultraestruturais do tecido em regeneração de animais em contato com a droga comparada com animais em condições normais, ou seja, sem contato com a droga em questão. Os animais em contato com a droga apresentaram a regeneração da actinotriquia de modo semelhante ao dos animais mantidos em condições normais, indicando que o naproxeno, na dose utilizada neste trabalho, não interferiu na síntese das actinotriquias durante o processo regenerativo da nadadeira caudal. Isto talvez seja porque o naproxeno não tenha influenciado a expressão dos genes necessários para o processo de regeneração, tal como o gene Sonic hedgehog (Shh), que está envolvido na formação da actinotriquia.Palavras-chave: nadadeira caudal, regeneração tecidual, elastoidina, droga anti-inflamatória não esteroide, peixe.

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In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage

Cited by 22 publications

References 52 publications

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Cyclooxygenase 2‐dependent prostaglandin E₂ modulates cartilage proteoglycan degradation in human osteoarthritis explants

The regeneration of the tail fin actinotrichia of carp (Cyprinus carpio, Linnaeus, 1758) under the action of naproxen

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In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage

Cited by 22 publications

References 52 publications

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Cyclooxygenase 2‐dependent prostaglandin E2 modulates cartilage proteoglycan degradation in human osteoarthritis explants

The regeneration of the tail fin actinotrichia of carp (Cyprinus carpio, Linnaeus, 1758) under the action of naproxen

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Cyclooxygenase 2‐dependent prostaglandin E₂ modulates cartilage proteoglycan degradation in human osteoarthritis explants