Research Article Improvement in orthopedic outcome score and reduction in IL-1β, CXCL13, and TNF-α in synovial fluid of osteoarthritis patients following arthroscopic knee surgery.

Li, Z.M.; Li, M.

doi:10.4238/gmr16039487

Cited by 10 publications

(5 citation statements)

References 19 publications

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“…IKKγ is known to be a regulatory subunit [13,27], and it may be poorly responsive to proin ammatory stimuli. It is known that OA synovial uid contains high levels of in ammatory cytokines such as IL-1β and TNFα [28,29], which is consistent with the results of this study showing increased protein expressions of IKKs in degenerated menisci and increased gene expressions of IKKs in meniscal cells in response to these in ammatory cytokines.…”

Section: Discussionsupporting

confidence: 92%

Targeting IKK epsilon to Prevent Meniscal Degeneration in Osteoarthritis: Insights from Human Tissue and Mouse Models

Hirose,

Akasaki,

Kuwahara

et al. 2024

Preprint

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Objective. Meniscal degeneration may precede or indicate early-stage osteoarthritis (OA); however, the pathogenetic involvement of the NF-κB pathway and its upstream IκB kinase (IKK) is unclear. This study investigated the functional role of IKK in the pathogenesis of meniscal degeneration, and the efficacy of IKKε inhibition as a therapeutic approach. Methods. IKK expression in normal and OA human menisci was analyzed immunohistochemically. Gain- or loss-of-function experiments were performed in human meniscal cells. Additionally, meniscal degeneration was induced in wild-type mice and treated with intraarticular injection of the IKKε inhibitors amlexanox and BAY-985 every 5 days for 4 weeks. Meniscal degeneration was also induced in IKKε knockout mice. Mice were subsequently examined histologically. Results. IKK protein expression was increased in human OA menisci. In vitro, the expression of meniscal degeneration–related factors was decreased after knockdown of each IKK, particularly IKKε, using small interfering RNA in human OA meniscal cells. Conversely, IKKε overexpression significantly increased the expression of these factors, and amlexanox and BAY-985 canceled this effect. Western blot analysis showed that IKKε overexpression increased IκBα and p65 phosphorylation. In vivo, both IKKε deletion and intraarticular injection of IKKε inhibitors protected mouse menisci against degeneration. Conclusion. These results indicate that IKKs are involved in meniscal degeneration when it constitutes the preliminary or early stage of OA, with IKKε possibly playing a significant role. Furthermore, IKKε regulates meniscal degeneration through NF-κB signaling–mediated catabolism. Two IKKε inhibitors, amlexanox and BAY-985, are potential targets for the treatment of meniscal degeneration prior to OA.

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Section: Discussionsupporting

confidence: 92%

Targeting IKK epsilon to Prevent Meniscal Degeneration in Osteoarthritis: Insights from Human Tissue and Mouse Models

Hirose,

Akasaki,

Kuwahara

et al. 2024

Preprint

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“…29 The chemokine CXCL13, upregulated in the PS-and PCS-treated groups after 48 h in the present study, might contribute to a catabolic state as it reportedly increases in the synovial fluid of OA patients with severe cartilage damage, whereas reduced levels are found after surgery. 30,31 IL-1RII serves as an inhibitor of IL-1 signalling, 32 and its increased expression after 48 h of stimulation suggests the potential of all treatments to reduce IL-1β signalling.…”

Section: Discussionmentioning

confidence: 99%

Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants

Löfgren

Ekman

Ekholm

et al. 2022

Equine Veterinary Journal

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Background: Autologous conditioned serum (ACS) is used to treat osteoarthritis in horses, although its effects are not fully investigated. Objectives: To investigate the effects of equine serum and conditioned serum on chondrocytes stimulated with interleukin (IL)-1β and cartilage explants with mild osteoarthritis. Study design: In vitro experimental study. Methods: The effect of three different serum preparations (unincubated control [PS], serum incubated 24 h [PS24h] and serum incubated 24 h in ACS containers [PCS])pooled from lame horses were tested in two in vitro models. IL-1β and IL-1 receptor antagonist (IL-1Ra) concentrations were measured in all sera. In model 1, chondrocyte pellet cultures were stimulated with IL-1β prior to treatment with the serum preparations for 2 and 48 h. Microarray, polymerase chain reaction, and matrix metallopeptidase-13 analyses were performed. In model 2, cartilage explants from horses with structural osteoarthritis were treated with PS or PCS on days 0, 6 and 12, or left untreated, and evaluated at day 24 using the OARSI grading scale for histological evaluation of articular cartilage. Results:The IL-1Ra concentration in PS24h and PCS was significantly higher than in PS. In model 1, inflammation-and cartilage matrix degradation-related genes were upregulated after 48 h in all treatment groups versus untreated controls. Cartilage matrix molecules, aggrecan and collagens, were downregulated in PS24h-and PCStreated pellets versus untreated controls. Growth factor signalling genes were upregulated-FGF7 in all treatment groups, BMP2 in PS24h-, and INHBA in PCStreated-compared with untreated controls. In model 2, the OARSI score at day 24 was not significantly different between treatment groups.Main limitations: Results from in vitro models cannot be directly translated to in vivo situations.

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“…TNFα occurs naturally during the development of inflammation in the human body and is produced mainly by immune cells; thus, it invokes a more physiological FLS inflammatory response [ 23 ]. Moreover, elevated levels of this factor are observed in the synovial fluid of OA patients [ 7 , 24 , 25 ]. This approach allowed us to obtain more convincing data regarding the response of FLS to inflammation and compare the pro-inflammatory effects of a substance widely used for modeling inflammation (LPS) with a more physiological cytokine (TNFα).…”

Section: Introductionmentioning

confidence: 99%

Inflammation-Driven Secretion Potential Is Upregulated in Osteoarthritic Fibroblast-Like Synoviocytes

Chwastek

Kędziora

Borczyk

et al. 2022

IJMS

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Osteoarthritis (OA) is one of the most common joint pathologies and a major cause of disability among the population of developed countries. It manifests as a gradual degeneration of the cartilage and subchondral part of the bone, leading to joint damage. Recent studies indicate that not only the cells that make up the articular cartilage but also the synoviocytes, which build the membrane surrounding the joint, contribute to the development of OA. Therefore, the aim of the study was to determine the response to inflammatory factors of osteoarthritic synoviocytes and to identify proteins secreted by them that may influence the progression of OA. This study demonstrated that fibroblast-like synoviocytes of OA patients (FLS-OA) respond more strongly to pro-inflammatory stimulation than cells obtained from control patients (FLS). These changes were observed at the transcriptome level and subsequently confirmed by protein analysis. FLS-OA stimulated by pro-inflammatory factors [such as lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) were shown to secrete significantly more chemokines (CXCL6, CXCL10, and CXCL16) and growth factors [angiopoietin-like protein 1 (ANGPTL1), fibroblast growth factor 5 (FGF5), and insulin-like growth factor 2 (IGF2)] than control cells. Moreover, the translation of proteolytic enzymes [matrix metalloprotease 3 (MMP3), cathepsin K (CTSK), and cathepsin S (CTSS)] by FLS-OA is increased under inflammatory conditions. Our data indicate that the FLS of OA patients are functionally altered, resulting in an enhanced response to the presence of pro-inflammatory factors in the environment, manifested by the increased production of the previously mentioned proteins, which may promote further disease progression.

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Research Article Improvement in orthopedic outcome score and reduction in IL-1β, CXCL13, and TNF-α in synovial fluid of osteoarthritis patients following arthroscopic knee surgery.

Cited by 10 publications

References 19 publications

Targeting IKK epsilon to Prevent Meniscal Degeneration in Osteoarthritis: Insights from Human Tissue and Mouse Models

Targeting IKK epsilon to Prevent Meniscal Degeneration in Osteoarthritis: Insights from Human Tissue and Mouse Models

Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants

Inflammation-Driven Secretion Potential Is Upregulated in Osteoarthritic Fibroblast-Like Synoviocytes

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