The influence of Celecoxib on matrix synthesis by chondrocytes under mechanical stress in vitro

Iimoto, Seiji; Watanabe, Shohei; Takahashi, Toshiaki; Shimizu, Akira; Yamamoto, Haruyasu

doi:10.3892/ijmm.16.6.1083

Cited by 9 publications

(15 citation statements)

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“…Chondrocytes attached 2–3 days after plating on deformable membranes and exhibited a polygonal and spread shape [ 13 , 26 , 33 , 34 ]. At confluence, cell layer displayed the characteristic “cobblestone” appearance [ 13 , 31 , 35 , 36 ]. Cells adhered well on the culture plate surface and were randomly orientated and distributed [ 35 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

Effects of Cyclic Tensile Strain on Chondrocyte Metabolism: A Systematic Review

et al. 2015

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Chondrocytes reorganize the extracellular matrix of articular cartilage in response to externally applied loads. Thereby, different loading characteristics lead to different biological responses. Despite of active research in this area, it is still unclear which parts of the extracellular matrix adapt in what ways, and how specific loading characteristics affect matrix changes. This review focuses on the influence of cyclic tensile strain on chondrocyte metabolism in vitro. It also aimed to identify anabolic or catabolic chondrocyte responses to different loading protocols. The key findings show that loading cells up to 3% strain, 0.17 Hz, and 2 h, resulted in weak or no biological responses. Loading between 3–10% strain, 0.17–0.5 Hz, and 2–12 h led to anabolic responses; and above 10% strain, 0.5 Hz, and 12 h catabolic events predominated. However, this review also discusses that various other factors are involved in the remodeling of the extracellular matrix in response to loading, and that parameters like an inflammatory environment might influence the biological response.

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Section: Resultsmentioning

confidence: 99%

Effects of Cyclic Tensile Strain on Chondrocyte Metabolism: A Systematic Review

et al. 2015

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“…, 2008). Moreover, selective inhibition of COX‐2 attenuated the degradation of matrix proteins induced by a mechanical load stimulus (Iimoto et al. , 2005).…”

Section: Discussionmentioning

confidence: 99%

Age-related differences in prostaglandin E2 synthesis by equine cartilage explants and synoviocytes

Briston¹,

Dudhia²,

Lees³

2009

Journal of Veterinary Pharmacology and Therapeutics

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Time- and concentration-related actions of lipopolysaccharide (LPS) on the synthesis of prostaglandin E(2) (PGE(2)) were investigated in cartilage explants and synoviocytes harvested from 3 age groups of horses, all with clinically normal joint function: group A <10 years; group B 11-20 years and group C >20 years. Cartilage explants from group A horses were least and those from group C were most sensitive to LPS. Significant increases in PGE(2) concentration (P

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“…Several studies indicate that at the nano-to micromolar concentrations produced by OA tissues, PGE 2 may exert catabolic effects (4, 24 -26). For example, the selective COX-2 inhibitor celecoxib has been reported to reverse the decrease of matrix proteins, collagen type II, and aggrecan induced by mechanical stress (27), whereas the addition of PGE 2 to cocultures of OA cartilage and synovial membrane abrogates the beneficial effects of COX-2 inhibitors on proteoglycan content (28). However, not all effects of PGE 2 generation may be detrimental.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Exerts Catabolic Effects in Osteoarthritis Cartilage: Evidence for Signaling via the EP4 Receptor

Attur

Al-Mussawir

Patel

et al. 2008

The Journal of Immunology

178

132

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Elevated levels of PGE2 have been reported in synovial fluid and cartilage from patients with osteoarthritis (OA). However, the functions of PGE2 in cartilage metabolism have not previously been studied in detail. To do so, we cultured cartilage explants, obtained from patients undergoing knee replacement surgery for advanced OA, with PGE2 (0.1–10 μM). PGE2 inhibited proteoglycan synthesis in a dose-dependent manner (maximum 25% inhibition (p < 0.01)). PGE2 also induced collagen degradation, in a manner inhibitable by the matrix metalloproteinase (MMP) inhibitor ilomastat. PGE2 inhibited spontaneous MMP-1, but augmented MMP-13 secretion by OA cartilage explant cultures. PCR analysis of OA chondrocytes treated with PGE2 with or without IL-1 revealed that IL-1-induced MMP-13 expression was augmented by PGE2 and significantly inhibited by the cycolooygenase 2 selective inhibitor celecoxib. Conversely, MMP-1 expression was inhibited by PGE2, while celecoxib enhanced both spontaneous and IL-1-induced expression. IL-1 induction of aggrecanase 5 (ADAMTS-5), but not ADAMTS-4, was also enhanced by PGE2 (10 μM) and reversed by celecoxib (2 μM). Quantitative PCR screening of nondiseased and end-stage human knee OA articular cartilage specimens revealed that the PGE2 receptor EP4 was up-regulated in OA cartilage. Moreover, blocking the EP4 receptor (EP4 antagonist, AH23848) mimicked celecoxib by inhibiting MMP-13, ADAMST-5 expression, and proteoglycan degradation. These results suggest that PGE2 inhibits proteoglycan synthesis and stimulates matrix degradation in OA chondrocytes via the EP4 receptor. Targeting EP4, rather than cyclooxygenase 2, could represent a future strategy for OA disease modification.

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The influence of Celecoxib on matrix synthesis by chondrocytes under mechanical stress in vitro

Cited by 9 publications

References 0 publications

Effects of Cyclic Tensile Strain on Chondrocyte Metabolism: A Systematic Review

Effects of Cyclic Tensile Strain on Chondrocyte Metabolism: A Systematic Review

Age-related differences in prostaglandin E2 synthesis by equine cartilage explants and synoviocytes

Prostaglandin E2 Exerts Catabolic Effects in Osteoarthritis Cartilage: Evidence for Signaling via the EP4 Receptor

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