Therapeutic options for targeting inflammatory osteoarthritis pain

Conaghan, Philip G.; Cook, Andrew D.; Hamilton, John A.; Tak, Paul P.

doi:10.1038/s41584-019-0221-y

Cited by 266 publications

(200 citation statements)

References 103 publications

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“…3,4 Many risk factors such as an increase in life expectancy, obesity and population ageing have contributed to the increase in the incidence of OA. 5 The mainstay for OA treatment includes pharmacological and nonpharmacological to improve function and reduce pain. However, these treatments for OA are directed at symptomatic response and do not affect structural alterations.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: lncRNA HAND2-AS1 is Down Regulated in Osteoarthritis and Regulates IL‐6 Expression in Chondrocyte

Zhou

Shen³

et al. 2020

Preprint

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Background: Osteoarthritis (OA) is a leading cause of disability. The incidence of OA is progressively rising due to the diminishing levels of physical activity and ever-expanding ageing population. However, the mainstay for OA treatment only can improve symptoms without delay the progression of this severe disease. This study aimed to explore the biological role and clinical function of lncRNA HAND2-AS1 in OA.Methods: Blood samples and synovial fluid were collected from OA patients and normal subjects. HAND2-AS1 expression was detected by qRT-PCR and IL-6 expression was detected by ELISA; The plasma levels of HAND2-AS1 were also detected in different ages, stages and gender of OA patients and controls. Furthermore, the ROC curve was used to analyze whether HAND2-AS1 can distinguish OA patients from normal subjects. Also, Pearson correlation coefficient analysis was used to analyze the correlation between lncRNA HAND2-AS1 and IL-6. In addition, western blot was used to detect the IL-6 level upon HAND2-AS1 overexpression in chondrocytes and qRT-PCR was used to detect the HAND2-AS1 level after endogenous IL-6 treatment. Results: HAND2-AS1 and IL-6 were dysregulated in plasma and synovial fluid of OA patients. The expression of HAND2-AS1 in plasma of OA patients was decreased with aging and progression. Furthermore, HAND2-AS1 downregulation effectively distinguished OA patients from the healthy controls. Overexpression of HAND2-AS1 inhibited IL‐6 expression in chondrocytes, while treatment with exogenous IL‐6 did not affect HAND2-AS1 expression. Conclusion: HAND2-AS1 effectively distinguished OA patients from the healthy controls and regulates IL‐6 expression in human chondrocytes. Abbreviations: Long non-coding RNA, lncRNA; Osteoarthritis, OA; Interleukin 6, IL‐6; Negative control plasmid, NC; Real‐time quantitative polymerase chain reaction, qRT-PCR; Enzyme‐linked immunosorbent assay, ELISA; Receiver operating characteristic curve, ROC; Trial registration: ChiCTR, ChiCTR2000038635. Registered 11 February 2019, http:// http://www.chictr.org.cn/ ChiCTR2000038635

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: lncRNA HAND2-AS1 is Down Regulated in Osteoarthritis and Regulates IL‐6 Expression in Chondrocyte

Zhou

Shen³

et al. 2020

Preprint

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“…To date, there are few clinical studies in humans considering macrophage polarization and osteoarthritis (27,34,50,52). Most of them do not access macrophage polarization and when they access, they are in vitro studies with human cells.…”

Section: Macrophages In Oamentioning

confidence: 99%

Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

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“…Prior work has shown that methotrexate, a commonly used disease‐modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA), in part exerts its antiinflammatory effect by increasing extracellular adenosine levels (23). There is minimal data evaluating this pathway in humans with OA; however, preliminary data from The Pain Reduction with Oral Methotrexate in knee Osteoarthritis (PROMOTE) trial suggests that methotrexate may improve OA symptoms as well (24).…”

Section: Discussionmentioning

confidence: 99%

Reduction in Osteoarthritis Risk After Treatment With Ticagrelor Compared to Clopidogrel: A Propensity Score–Matching Analysis

Baker

Weng

Robinson

et al. 2020

Arthritis & Rheumatology

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Objective Osteoarthritis (OA) is a common cause of joint pain and disability, and effective treatments are lacking. Extracellular adenosine has antiinflammatory effects and can prevent and treat OA in animal models. Ticagrelor and clopidogrel are both used in patients with coronary artery disease, but only ticagrelor increases extracellular adenosine levels. This study was undertaken to determine whether treatment with ticagrelor was associated with a lower risk of OA. Methods We conducted a 1:2 propensity score–matching analysis using data from 2011–2017 in the Optum Clinformatics Data Mart. Patients who had received either ticagrelor or clopidogrel for ≥90 days were included in our study, and patients with a prior diagnosis of OA or inflammatory arthritis were excluded. OA was identified using International Classification of Diseases codes. The primary outcome was the time to diagnosis of OA after treatment with ticagrelor versus clopidogrel. Results Our propensity score–matched cohort consisted of 7,007 ticagrelor‐treated patients and 14,014 clopidogrel‐treated patients, with a median number of days receiving treatment of 287 and 284, respectively. For both groups, the mean age was 64 years, and 73% of the patients were male. Multivariate Cox regression analysis estimated a hazard ratio for developing OA of 0.71 (95% confidence interval 0.64–0.79) (P < 0.001) after treatment with ticagrelor compared to clopidogrel. Conclusion Treatment with ticagrelor was associated with a 29% lower risk of developing OA compared to treatment with clopidogrel over 5 years of follow‐up. We hypothesize that the reduction in OA seen in patients who received ticagrelor may in part be due to increased extracellular adenosine levels.

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Therapeutic options for targeting inflammatory osteoarthritis pain

Cited by 266 publications

References 103 publications

WITHDRAWN: lncRNA HAND2-AS1 is Down Regulated in Osteoarthritis and Regulates IL‐6 Expression in Chondrocyte

WITHDRAWN: lncRNA HAND2-AS1 is Down Regulated in Osteoarthritis and Regulates IL‐6 Expression in Chondrocyte

Macrophage: A Potential Target on Cartilage Regeneration

Reduction in Osteoarthritis Risk After Treatment With Ticagrelor Compared to Clopidogrel: A Propensity Score–Matching Analysis

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