Does long term colchicine prevent degradation of collagen fiber network in osteoarthritis?

Srivastava, Ragini; Das, Siddharth Kumar; Goel, Gautam; Asthana, Abhas; Agarwal, Gaurav

doi:10.1111/1756-185x.13022

Cited by 6 publications

(9 citation statements)

References 16 publications

(12 reference statements)

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“…In experimental arthritis in mice, neutrophils and natural killer cells interact to promote arthritis following intraarticular collagenase injection (20). Colchicine, which inhibits neutrophil production of superoxide and neutrophil adhesion, mobilization, recruitment, and chemotaxis (21), has to date yielded both positive results (22)(23)(24)(25) and negative results (26) in clinical trials evaluating the treatment of OA symptoms or progression.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression

Hsueh

Zhang

Wellman

et al. 2020

Arthritis & Rheumatology

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Objective. To evaluate the role of immune cells and their effector cytokines in the pathogenesis and progression of knee osteoarthritis (OA) in matched OA synovial fluid (SF) and synovial tissue samples. Methods. Cells from matched samples of synovial tissue and SF acquired from individuals undergoing total knee replacement for OA (n = 39) were characterized for immune cell-associated surface markers and intracellular cytokine expression using polychromatic flow cytometry. Additional individuals with radiographic knee OA (Kellgren/Lawrence severity grades ≥1) who had available etarfolatide (inflammatory cell) imaging (n = 26) or baseline and 3-year data on progression of radiographic knee OA (n = 85) were also assessed. SF cytokine concentrations in all cohorts were evaluated for associations with synovial tissue and SF cell phenotypes and severity of radiographic knee OA. Results. Macrophages (predominant in the synovial tissue, 53% of total cells) and neutrophils (predominant in the SF, 26% of total cells) were the major immune cell populations identified in the OA knee joints, exhibiting expression of or association with transforming growth factor β1 (TGFβ1) and elastase, respectively, in the SF. Expression levels of TGFβ1 and elastase were significantly associated with severity of radiographic knee OA. Baseline SF concentrations of TGFβ1 and elastase along with radiographic knee OA severity scores were predictive of knee OA progression, with areas under the receiver operating characteristic curves of 0.806 (for TGFβ1), 0.810 (for elastase), and 0.846 (for both TGFβ1 and elastase combined), with greater stability of prediction when both markers were utilized. Conclusion. Our findings demonstrate the hitherto underappreciated role of neutrophils in the sterile inflammatory process and progression of OA. Two soluble mediators, SF elastase and TGFβ1, are strong predictors of knee OA progression, reflecting a synergistic role of neutrophil and macrophage populations in the pathogenesis and worsening of OA that could potentially be utilized to identify patients who may have a greater risk of more rapid disease progression.

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Section: Introductionmentioning

confidence: 99%

Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression

Hsueh

Zhang

Wellman

et al. 2020

Arthritis & Rheumatology

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“…Furthermore, pooled evidence-that was of moderate quality-suggested that colchicine demonstrated only a small (SMD: 0.3) and statistically nonsignificant improvement in pain and physical dysfunction compared to the control group for patients with knee OA. [36] Limited evidence was reported assessing the effect of colchicine on biochemical markers [14,15,35] and imaging markers [14,15] in knee OA patients. Two of the three available trials studying QoL demonstrated superior improvements with colchicine treatment compared to control; however, both studies used non-validated generic PRO instruments not specifically developed for knee OA [9,12].…”

Section: Discussionmentioning

confidence: 99%

Section: Osteoarthritis-related Biochemical Markersmentioning

confidence: 99%

“…Three studies assessed biochemical markers of OA, including the one-hand OA study [14,15,35]. In knee OA patients, Srivastava et al reported a significant increase in serum COMP levels from 2 months to 1 year of follow-up in the paracetamol-alone group, while it remained stable in the colchicine group [35]. In another study in knee OA patients, serum levels of hs-CRP and synovial fluid levels of CTX-I were significantly reduced in the colchicine but not the placebo-treated arm over a 4-month follow-up [14].…”

Section: Osteoarthritis-related Biochemical Markersmentioning

confidence: 99%

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Efficacy and safety of colchicine for the treatment of osteoarthritis: a systematic review and meta-analysis of intervention trials

et al. 2022

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Objective Colchicine, an approved treatment for gout, has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, its efficacy and safety remain unclear in OA. This systematic review and meta-analysis evaluated the efficacy and safety of colchicine for the treatment of OA. Methods PubMed, Web of Science, Scopus, and Cochrane Central were searched from inception through September 2022. Two reviewers independently screened for randomized controlled trials (RCTs) comparing colchicine with placebo or other active comparators for the treatment of OA (knee, hand, or hip OA), extracted data, and performed Cochrane risk of bias assessments. Result Nine RCTs for the knee OA and one for the hand OA were identified, consisting of 847 patients (429 in colchicine arms, 409 in control arms). The studies were conducted between 2002 and 2021 with follow-up periods ranging from 2 to 12 months, in India, Iran, Turkey, Australia, Singapore, and Iraq. Moderate-quality evidence showed no clinically important pain reduction with colchicine compared to control (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], − 0.55, 0.22). Moderate-quality evidence showed no improvement in function with colchicine compared to control in knee OA patients (SMD, − 0.37; 95% CI, − 0.87, 0.13). Colchicine showed an acceptable safety profile with AEs/SAEs comparable to control. Conclusion Current evidence does not suggest a benefit of colchicine in reducing pain and improving physical function in the overall cohort of hand/knee OA patients. Future trials should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine. Graphical abstract Key Points•Colchicine is an approved treatment for gout that has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, the benefit and harms of colchicine in OA remain unclear.• Current evidence from randomized control trials does not suggest a benefit of colchicine in reducing pain and improving physical function for the treatment of OA patients.• Future trials of colchicine in OA should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine.

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“…Osteoarthritis (OA) is the most prevalent type of arthritis, and it is characterized by a progressive degradation of articular cartilage, new bone formation and acute inflammation (1). Knee osteoarthritis (KOA) with hip osteoarthritis is primarily responsible for the pain and locomotor disability worldwide (2,3).…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase‑13, NF‑κB p65 and interleukin‑1β are associated with the severity of knee osteoarthritis

Zhao¹,

Lin²,

Guo³

et al. 2020

Exp Ther Med

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Knee osteoarthritis (KOA) is a prevalent disease, especially in the elderly. The present study examined the expression of matrix metalloproteinase-13 (MMP-13), NF-κBp65 and interleukin (IL)-lβ in the synovial tissues of KOA patients and the role of MMP-13 and the NF-κBp65 signalling pathway in KOA pathogenesis. A total of 100 KOA patients were enrolled in our hospital from December 2015 to December 2017 and were classified into either a mild KOA group (Outerbridge grade 1 and 2) or a severe KOA group (Outerbridge grade 3 and 4). Non-OA patients were included as controls. Synovial tissues from patients in both groups were collected for detection of the mRNA and protein expression of MMP-13, NF-κBp65 and IL-lβ. Synovial tissue slices were subjected to haematoxylin and eosin staining and immunohistochemistry (SP method). Cartilage tissues were observed under a light microscope after Safranin O-fast green staining. Reverse transcription-quantitative PCR and western blot analyses demonstrated that the expression of MMP-13, NF-κBp65 and IL-lβ in the mild and severe groups were substantially upregulated compared with the control group (all P<0.05). A positive correlation between MMP-13 and NF-κBp65 expression in the KOA synovial tissues was identified (P<0.05). Immunohistochemistry revealed that the expression of MMP-13 and NF-κBp65 was related to the severity of KOA 92.54%; moderate, 76.52%; control: 32.14%; 85.56%; moderate, 48.12%; control: 28.32%). This evidence indicated that the severity of KOA was related to MMP-13 and NF-κBp65 expression. The NF-κB signalling pathway may be activated during OA progression, which could upregulate the expression of MMP-13 and IL-1β and accelerate the deterioration of articular cartilage.

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Does long term colchicine prevent degradation of collagen fiber network in osteoarthritis?

Cited by 6 publications

References 16 publications

Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression

Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression

Efficacy and safety of colchicine for the treatment of osteoarthritis: a systematic review and meta-analysis of intervention trials

Matrix metalloproteinase‑13, NF‑κB p65 and interleukin‑1β are associated with the severity of knee osteoarthritis

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