Effects of Prescription Nonsteroidal Antiinflammatory Drugs on Symptoms and Disease Progression Among Patients With Knee Osteoarthritis

Lapane, Kate L.; Yang, Shibing; Driban, Jeffrey B.; Liu, Shao‐Hsien; Dubé, Catherine; McAlindon, Timothy E.; Eaton, Charles B.

doi:10.1002/art.38933

Cited by 56 publications

(64 citation statements)

References 34 publications

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“…Current therapy for OA is based on a sequential hierarchical approach, with non-steroidal anti-inflammatory drugs (NSAIDs) as the leading treatment option [3]. Although they exhibit effective pain reduction, the treatment with NSAIDs is limited by complications such as gastroenteropathy, ease of suppression, limited clinical remission rate, immunity, and secondary tumors [4, 5]. An alternative is natural anti-inflammatory agents derived from plants and herbs, such as olive oil, icariin, and angelica polysaccharides, which have potential to prevent cartilage degeneration in patients with OA [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Zhong

Liang

Yao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA.

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Section: Introductionmentioning

confidence: 99%

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Zhong

Liang

Yao

et al. 2018

Cell Physiol Biochem

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“…These results are in line with certain anti-inflammatory agents moderately reducing certain OA symptoms. 15,72 However, more detailed studies over longer time periods will be required to understand the mechanisms through which OAC-NM interactions differ from OAC-AM interactions.…”

Section: Toward Modulating Inflammation: Comparison Of Oac-am and Oac-nmmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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“…However, many in vitro studies investigating NSAID use showed decreased proteoglycan and collagen production in articular chondrocytes [11, [12, [13, [14]. Clinically there is a concern that NSAID use may increase progression of osteoarthritis (OA) over time [15, [16, [17, [18]. …”

Section: Introductionmentioning

confidence: 99%

NSAID use in intervertebral disc degeneration: what are the effects on matrix homeostasis in vivo?

et al. 2017

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Background Context Non-steroidal anti-inflammatory (NSAID) agents are a widely utilized treatment for low back pain (LBP). Literature on NSAID use in articular cartilage has shown detrimental effects; however, minimal data exist to detail the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a major cause of LBP, we explored the effects of indomethacin, a commonly used NSAID, on disc matrix homeostasis in an animal model of IDD. Purpose To determine the effects of oral indomethacin administration on IDD in an in vivo rabbit model. This study hypothesized that indomethacin use would accelerate the progression of IDD based upon serial imaging and tissue outcomes. Study Design/Setting This was a laboratory-based, controlled, in vivo evaluation of the effects of oral indomethacin administration on rabbit intervertebral discs. Methods Six skeletally mature New Zealand White rabbits were divided into two groups: disc puncture alone to induce IDD (Puncture group) and disc puncture plus indomethacin (Punc+Ind group). The Punc+Ind group received daily administration of 6mg/kg oral indomethacin. Serial magnetic resonance imaging (MRI) were obtained at 0, 4, 8, and 12 weeks. MRI index and nucleus pulposus (NP) area were calculated. Discs were harvested at 12 weeks for determination of disc glycosaminoglycan (GAG) content, relative gene expression measured by real time polymerase chain reaction, and histological analyses. Results MRI index and NP area of punctured discs in the Punc+Ind group demonstrated no worsening of degeneration compared to the Puncture group. Histological analysis was consistent with less severe disc degeneration in the Punc+Ind group. Minimal differences in gene expression of matrix genes were observed between Puncture and Punc+Ind groups. GAG content was higher in animals receiving indomethacin in both annulus fibrosus (AF) and NP at adjacent uninjured discs. Conclusions Oral indomethacin administration did not result in acceleration of IDD in an in vivo rabbit model. Future research is needed to ascertain long-term effects of indomethacin and other NSAIDs on disc matrix homeostasis.

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Effects of Prescription Nonsteroidal Antiinflammatory Drugs on Symptoms and Disease Progression Among Patients With Knee Osteoarthritis

Cited by 56 publications

References 34 publications

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

NSAID use in intervertebral disc degeneration: what are the effects on matrix homeostasis in vivo?

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