Cytokines in the pathogenesis of hemophilic arthropathy

Wojdasiewicz, Piotr; Poniatowski, Łukasz A.; Nauman, Paweł; Mandat, Tomasz; Paradowska‐Gorycka, Agnieszka; Romanowska-Próchnicka, Katarzyna; Szukiewicz, Dariusz; Kotela, Andrzej; Kubaszewski, Łukasz; Kotela, Ireneusz; Kurkowska‐Jastrzębska, Iwona; Gasik, Robert

doi:10.1016/j.cytogfr.2017.11.003

Cited by 45 publications

(65 citation statements)

References 136 publications

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“…To the best of our knowledge, this is the first study to compare the changes of synovium, cartilage and subchondral bone separately among different age groups using MSKUS. These findings are comparable to those of previous studies demonstrating that osteochondral damages are irreversible 25,26. In our study, the synovium subscores are low in all the three index joints in childhood, indicating reversible synovial hypertrophy at an early stage of HA.…”

supporting

confidence: 91%

“…These findings are comparable to those of previous studies demonstrating that osteochondral damages are irreversible. 25,26 Moreover, in view of the finding that the majority of severe and moderate HAs develop before 30 years of age, it may be rational to highlight improved access to medical resources for these patients. Mean joint scores of seven patients undergoing 'on-demand to prophylactic replacement therapy' were analysed, and no significant recovery from HA was found in comparison with those who received on-demand therapy, indicating unsatisfying efficacy of this strategy.…”

Section: Discussionmentioning

confidence: 99%

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Age‐related severity and distribution of haemophilic arthropathy of the knee, ankle and elbow among Chinese patients with haemophilia

et al. 2019

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Introduction and aims Age‐related severity and distribution of haemophilic arthropathy (HA) among Chinese patients with haemophilia using the Haemophilia Early Detection with Ultrasound (HEAD‐US) system have not been extensively studied. Methods In our study, 89 patients with moderate and severe haemophilia were recruited. A total of 534 joints (knees, ankles and elbows on both sides included) were evaluated using musculoskeletal ultrasound (MSKUS) and scored using the HEAD‐US system. Results Prevalence and average number of HA were 39.1% and 0.7, 90.6% and 3.2, 94.1% and 4.5, and 100% and 4.3 for ages ≤10, 11‐20, 21‐30 and 31‐40 years, respectively. Prevalence and mean number of knee, ankle and elbow arthropathies also increased with age, although joint damages progressed in unparallel patterns. A significant difference in synovium subscores was observed between patients aged <10 and >10 years. An increasing tendency was observed in cartilage and subchondral bone subscores along with age before 30 years. No significant difference in mean joint scores was found between patients receiving on‐demand therapy and those receiving on‐demand to low‐dose prophylactic therapy. Conclusions Haemophilic arthropathy developed in early childhood and progressed mainly before 30 years of age among Chinese patients with haemophilia, although in different ways among the knee, ankle and elbow.

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supporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Age‐related severity and distribution of haemophilic arthropathy of the knee, ankle and elbow among Chinese patients with haemophilia

et al. 2019

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“…Pro-inflammatory cytokines have been reported to be involved in the pathogenesis of synovitis [25,28] as interactions within the cytokine network and other inflammatory mediators in the affected joint can create an inflammatory environment. Theoretically, an anti-cytokine approach can be used to protect against bleeding in damaged joints; however, limited studies have shown that intervention of the cytokine network may serve as a novel therapeutic direction [5,[29][30][31]; this includes our previous study with anti-IL-6 in hemophilia A mice [8].…”

Section: Discussionmentioning

confidence: 99%

A Translational Study of TNF-Alpha Antagonists as an Adjunctive Therapy for Preventing Hemophilic Arthropathy

Zhang

Yang

et al. 2019

JCM

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Repeated intra-articular hemorrhages lead to hemophilic arthropathy in severe hemophilia. Inflammation and pro-inflammatory cytokines (e.g., tumor necrosis factor alpha (TNFα)) might be involved in this pathogenesis. We hypothesized that anti-TNFα may provide adjuvant protection for hemophilic arthropathy management. We measured TNFα in synovial lavage from hemophilia mice subjected to hemarthrosis induction and synovial fluid from patients with hemophilic arthropathy (n = 5). In hemophilia mice, recurrent hemarthroses were induced, anti-TNFα was initiated either from day (D)7 after one hemarthrosis episode or D21 after three hemarthroses episodes (n ≥ 7/treatment group). In patients with hemophilic arthropathy (16 patients with 17 affected joints), a single dose of anti-TNFα was administered intra-articularly. Efficacy, characterized by synovial membrane thickness and vascularity, was determined. Elevated TNFα in synovial lavage was found in the hemophilia mice and patients with hemophilic arthropathy. Hemophilia mice subjected to three hemarthroses developed severe synovitis (Synovitis score of 6.0 ± 1.6). Factor IX (FIX) replacement alone partially improved the pathological changes (Synovitis score of 4.2 ± 0.8). However, anti-TNFα treatment initiated at D7, not D21, significantly provided protection (Synovitis score of 1.8 ± 0.9 vs. 3.9 ± 0.3). In patients with hemophilic arthropathy, intra-articular anti-TNFα significantly decreased synovial thickness and vascularity during the observed period from D7 to D30. Collectively, this preliminary study seems to indicate that TNFα may be associated with the pathogenicity of hemophilic arthropathy and anti-TNFα could provide adjuvant protection against hemophilic arthropathy. Further studies are required to confirm the preliminary results shown in this study.

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“…In hemophilic arthropathy, pro-in ammatory cytokines such as interleukin (IL)-1β [6][7][8] and tumor necrosis factor (TNF)-α [6,9] are produced in the hemosiderin-laden synovial tissue, and these cytokines trigger catabolic programs, activating nitric oxide (NO) [1,6] and matrix metalloproteinase (MMP) expression [6], osteoarthritis [10], and rheumatoid arthritis. These cytokines also increase iron uptake into monocytes and synovial broblasts and accelerate the vicious cycle of synovitis [7].…”

Section: Introductionmentioning

confidence: 99%

Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model

Sogi

Yabe

Hagiwara

et al. 2020

Preprint

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Background: Joint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorders such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis and oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although it is apparent that joint hemorrhage has negative effects on the articular cartilage, there is no consensus whether a reduction in joint hemorrhage is effective to prevent articular cartilage degeneration. The purpose of this study was to investigate the articular cartilage degeneration induced by a combination of joint hemorrhage and joint immobilization in a rat immobilized knee model. Methods: The knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were randomly divided into the following groups: immobilized blood injection (Im-B) and immobilized-normal saline injection (Im-NS) groups. The cartilage was evaluated in two areas (contact and non-contact areas). The cartilage was used to assess chondrocyte count, Modified Mankin score, and cartilage thickness. The total RNA was extracted from the cartilage in both areas, and the expression of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was measured by quantitative real-time polymerase chain reaction. Results: The number of chondrocytes in the Im-B group significantly decreased in both areas, compared with that in the Im-NS group. Modified Mankin score from 4–8 weeks of the Im-B group was significantly higher than that of the Im-NS group only in the contact area. The expression of MMP-8 and MMP-13 from 2 to 4 weeks and TNF-α from 2 to 8 weeks significantly increased in the Im-B group compared with those in the Im-NS group, but there was no significant difference in IL-1β expression. Conclusions: The results showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Drainage of a joint hemorrhage or avoidance of loading may help prevent cartilage degeneration during joint immobilization with a hemorrhage.

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Cytokines in the pathogenesis of hemophilic arthropathy

Cited by 45 publications

References 136 publications

Age‐related severity and distribution of haemophilic arthropathy of the knee, ankle and elbow among Chinese patients with haemophilia

Age‐related severity and distribution of haemophilic arthropathy of the knee, ankle and elbow among Chinese patients with haemophilia

A Translational Study of TNF-Alpha Antagonists as an Adjunctive Therapy for Preventing Hemophilic Arthropathy

Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model

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