Transforming growth factor activating kinase 1 regulates extracellular matrix degrading enzymes and pain-related molecule expression following tumor necrosis factor-α stimulation of synovial cells: an in vitro study

Uchida, Katsuhisa; Takano, Shotaro; Matsumoto, Toshihide; Nagura, Naoshige; Inoue, Gen; Itakura, Makoto; Miyagi, Masayuki; Aikawa, Jun; Iwase, Dai; Minatani, Atsushi; Fujimaki, Hisako; Takaso, Masashi

doi:10.1186/s12891-017-1648-4

Cited by 23 publications

(18 citation statements)

References 38 publications

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“…Nevertheless, the patients not only reported improvement in UC-associated symptoms but also in CED-associated bone pain. Several studies have described a local effect of TNFα by induction of extracellular matrix degrading enzymes and pain-related molecule expression, a process regulated by transforming growth factor-β-activated kinase 1 (TAK-1), a member of the mitogen-activated protein kinase family 11. TNFα also seems to trigger hypernociception through changed pain processing in the central nervous system 12.…”

Section: Discussionmentioning

confidence: 99%

Pain improvement in Camurati-Engelmann disease after anti-TNFα therapy

Moreira¹,

Cunha

Jesus

et al. 2017

BMJ Case Reports

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Camurati-Engelmann disease (CED) is a rare disorder included in the group of craniotubular hyperostosis diseases. Corticosteroids are used for pain management in CED, but in refractory or corticosteroid-non-tolerant patients, pain management is limited. We report the case of a woman with CED diagnosed in early infancy whose initial complaints included persistent bone pain associated with progressive functional disability. She was treated with steroids but over time became dependent on higher doses with only mild pain relief. In her third decade, she was diagnosed with ulcerative colitis (UC) and was treated with mesalazine, azathioprine and prednisolone. Due to recurrent exacerbations of UC, treatment was changed to infliximab, an antitumour necrosis factor-alpha (TNFα). Remission of UC was achieved and CED-associated pain also improved with infliximab. This is the first report showing a possible role of anti-TNFα in pain management in CED with unsatisfactory response to steroids.

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Section: Discussionmentioning

confidence: 99%

Pain improvement in Camurati-Engelmann disease after anti-TNFα therapy

Moreira¹,

Cunha

Jesus

et al. 2017

BMJ Case Reports

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“…It has been reported that inhibition of TAK1 through siRNA could reduce the expression of MMP13, MMP1, and TNF-α induced by IL-1β [41]. The expression of COX-2, MMP-3, MMP-13, and ADAMTS-4 were reduced by injecting TAK1 inhibition in injured porcine cartilage [42]. In the present study, western blot con rmed that expression of TAK1 in the OA group was signi cantly higher than in the normal group in human cartilage tissues.…”

Section: Discussionmentioning

confidence: 94%

Effects of IL-1β-induced ADAMTS-4/-5 and TAK1 on the degradation of cartilage aggrecan in the progression of human osteoarthritis

Zhang

Fang

et al. 2020

Preprint

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Objective Interleukin-1β (IL-1β) is a potentially important cytokine involved in several pathological processes of osteoarthritis (OA). It is well known that a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4/-5) and transforming growth factor-β activated kinase 1 (TAK1) contribute to the degradation of human OA cartilage aggrecan. The purpose of this study was to investigate the mechanism by which IL-1β induced the expression of ADAMTS-4/-5 and TAK1 in human OA cartilage aggrecan degradation. Methods The pathological changes of cartilage tissues and chondrocytes were observed by histomorphological analysis. OA chondrocytes were isolated from human articular cartilage tissues and stimulated with 10 ng/ml of IL-1β at the per-designed times (24 h, 48 h, 72 h). Expression of ADAMTS-4/-5 and TAK1 in cartilage tissues and chondrocytes were measured using immunohistochemistry (IHC) and Western blot (WB). Results The level of IL-1β in synovial fluid in the normal group was significantly lower than that in OA group. The expression of ADAMTS-4/-5 and TAK1 were simultaneously upregulated in human OA cartilage tissues,and ADAMTS-4 was more positively correlated with TAK1 than ADAMTS-5. Furthermore, the expression of ADAMTS-4/-5 and TAK1 were increased by stimulation with IL-1β in human OA chondrocytes, but no positive correlation was found. Conclusion It is proposed that reducing the expression of ADAMTS-4/-5 in prevention of OA may involve the inhibition of TAK1 activity.

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“…To investigate the regulation of apelin by VEGF, SMCs harvested from six patients were stimulated with 1 ng/mL or 10 ng/mL VEGF for 24 h. Using methodology described elsewhere [ 48 ], SMCs were lysed in radioimmunoprecipitation buffer (Thermo Fisher Scientific) containing a protease inhibitor cocktail (Sigma-Aldrich, St. Louis MO, USA). Protein concentration was determined for each cell extract using a bicinchoninic acid (BCA) assay (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

Vascular endothelial growth factor expression and their action in the synovial membranes of patients with painful knee osteoarthritis

Takano

Uchida

Inoue

et al. 2018

BMC Musculoskelet Disord

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BackgroundResearch suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear.MethodsWe harvested synovial membrane (SM) from 102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence [K/L] grade 2–4) during total knee arthroplasty. Patients scored their pain on a 0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) were compared. Correlations between VAS and VEGF mRNA expression were investigated. To investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF and the neuropeptide apelin was determined by immunohistochemical analyses. To investigate the role of VEGF in regulating apelin expression, SM cells were exposed to VEGF.ResultsVEGF expression in the VAS ≥ 6 group was significantly greater than expression in the VAS < 6 group. Expression levels of VEGF were also positively correlated with VAS. VEGF-positive cells were identified in the lining of the SM. Expression of apelin mRNA and protein were significantly elevated in SM cells treated with exogenous VEGF compared to those treated with vehicle.ConclusionSynovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin.

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Transforming growth factor activating kinase 1 regulates extracellular matrix degrading enzymes and pain-related molecule expression following tumor necrosis factor-α stimulation of synovial cells: an in vitro study

Cited by 23 publications

References 38 publications

Pain improvement in Camurati-Engelmann disease after anti-TNFα therapy

Pain improvement in Camurati-Engelmann disease after anti-TNFα therapy

Effects of IL-1β-induced ADAMTS-4/-5 and TAK1 on the degradation of cartilage aggrecan in the progression of human osteoarthritis

Vascular endothelial growth factor expression and their action in the synovial membranes of patients with painful knee osteoarthritis

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