Biologic drugs as analgesics for the management of osteoarthritis

Dimitroulas, Theodoros; Lambe, Tosin; Klocke, Rainer; Kitas, George D.; Duarte, Rui

doi:10.1016/j.semarthrit.2016.12.001

Cited by 20 publications

(10 citation statements)

References 48 publications

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“…Short-term treatment with adalimumab for 12 weeks in patients with inflammatory OA resulted in clinical benefit in the majority of patients using the OARSI/OMERACT responder index [155]. However, there are two studies showing that it was not effective in patients with hand OA [156]. Interestingly, etanercept treatment in patients with erosive OA of the hands provided promising results regarding the ability of this drug to improve pain and modify structural damage [156].…”

Section: Ifp-synovial Membrane Mediators Involved In Oa Pathology mentioning

confidence: 99%

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Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain

Belluzzi

Stocco

Pozzuoli

et al. 2019

BioMed Research International

132

124

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Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA.

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Section: Ifp-synovial Membrane Mediators Involved In Oa Pathology mentioning

confidence: 99%

“…However, there are two studies showing that it was not effective in patients with hand OA [156]. Interestingly, etanercept treatment in patients with erosive OA of the hands provided promising results regarding the ability of this drug to improve pain and modify structural damage [156].…”

Section: Ifp-synovial Membrane Mediators Involved In Oa Pathology mentioning

confidence: 99%

Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain

Belluzzi

Stocco

Pozzuoli

et al. 2019

BioMed Research International

132

124

View full text Add to dashboard Cite

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“…This together with genetic and epigenetic factors of RA FLS [ 8 ] might explain the differences in the degree of synovial activation and inflammation in the two diseases. Interestingly, treatment with anti-TNF agents has failed to provide symptomatic benefits in OA trials [ 34 ] but a recent study also suggests analgesic efficacy of MTX in OA [ 35 ]. It is important to point out that the RA synovial samples in this study were obtained from patients with end-stage disease and it is possible that the differences in results between RA and OA FLS would have been larger in FLS from early RA.…”

Section: Discussionmentioning

confidence: 99%

Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rheumatoid arthritis fibroblast-like synoviocytes

2018

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BackgroundA key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro.MethodsPrimary FLS from patients with RA or osteoarthritis were stimulated with the mitogen platelet-derived growth factor (PDGF) and the cytokine interleukin-1β (IL-1β) in the presence or absence of MTX. Cells were then subjected to qPCR for gene expression and cell cycle analysis by flow cytometry.ResultsStimulation with PDGF and IL-1β increased the percentage of FLS in the G2/M phase and shifted the cell morphology to a dendritic shape. These effects were inhibited by MTX. Furthermore, PDGF + IL-1β reduced LBH mRNA expression. However, MTX treatment yielded significantly higher transcript levels of LBH, and of CDKN1A (p21) and TP53 (p53), compared to untreated samples upon mitogen stimulation. The expression of DNA methyltransferase-1 (DNMT1) was also higher in the presence of MTX and there was strong correlation between DNMT1 and LBH expression.ConclusionsTherapeutic concentrations of MTX abolish the effects of PDGF and IL-1β on tumor suppressor expression and inhibit mitogen-promoted FLS proliferation. These data demonstrate novel and important effects of MTX on pathogenic effector cells in the joint, which might involve epigenetic mechanisms.

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“…Considering its central role in the initiation and progress of OA, inhibition of OA inflammation seems to be able to form the basis of such DMOADs. Several anti-inflammatory therapeutics, which targeting the key mediators like IL-1β, TNF, COX1, COX2, MMPs, and iNOS, have been tested in human OA, but till now the results are disappointing 1 , 19 – 24 . Since OA is a heterogeneous disease and a large number of inflammatory mediators are involved, targeting a single molecular could not inhibit OA effectively.…”

Section: Introductionmentioning

confidence: 99%

Targeting miR-18a sensitizes chondrocytes to anticytokine therapy to prevent osteoarthritis progression

Lian

Tao

et al. 2020

Cell Death Dis

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Inflammation participates in the development of OA and targeting inflammatory signaling pathways is a potential strategy for OA treatment. IL-1β is one of the most important inflammatory factors to trigger the activation of NF-κB signaling and accelerate OA progression, whereas OA patients could hardly benefit from inhibiting IL-1β in clinic, suggesting the importance to further explore the details of OA inflammation. We here showed that expression of miR-18a in chondrocytes was specifically induced in response to IL-1β in vitro as well as in rat model of OA during which NF-κB signaling was involved, and that nuclear-translocated p65 directly upregulated miR-18a expression at transcriptional level. Further, increased miR-18a mediated hypertrophy of chondrocytes, resulting in OA degeneration, by targeting TGFβ1, SMAD2, and SMAD3 and subsequently leading to repression of TGF-β signaling. And the level of serum miR-18a was positively correlated to severity of OA. Interestingly, other than IL-1β, pro-inflammation cytokines involving TNFα could also remarkably upregulate miR-18a via activating NF-κB signaling and subsequently induce chondrocytes hypertrophy, suggesting a pivotal central role of miR-18a in inflammatory OA progression. Thus, our study revealed a novel convergence of NF-κB and TGF-β signaling mediated by miR-18a, and a novel mechanism underlying inflammation-regulated OA dependent of NF-κB/miR-18a/TGF-β axis. Notably, in vivo assay showed that targeting miR-18a sensitized OA chondrocytes to IL-1β inhibitor as targeting IL-1β and miR-18a simultaneously had much stronger inhibitory effects on OA progression than suppressing IL-1β alone. Therefore, the diagnostic and therapeutic potentials of miR-18a for OA were also revealed.

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Biologic drugs as analgesics for the management of osteoarthritis

Cited by 20 publications

References 48 publications

Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain

Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain

Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rheumatoid arthritis fibroblast-like synoviocytes

Targeting miR-18a sensitizes chondrocytes to anticytokine therapy to prevent osteoarthritis progression

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