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IL-40 is up-regulated in the synovial fluid and cartilage of osteoarthritis patients and contributes to the alteration of chondrocytes phenotype in vitro

LA. Cerezo, A. Navrátilová, M. Kuklová, A. Prokopcová, J. Baloun, T. Kropáčková, D. Veigl, S. Popelka, P. Fulín, R. Ballay, K. Pavelka, J. Vencovský, L. Šenolt

. 2024 ; 26 (1) : 146. [pub] 20240730

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24019653

Grant support
NU21-05-00276 Ministerstvo Zdravotnictví Ceské Republiky
NU21-05-00276 Ministerstvo Zdravotnictví Ceské Republiky
NU21-05-00276 Ministerstvo Zdravotnictví Ceské Republiky
RVO 00023728 Ministerstvo Zdravotnictví Ceské Republiky
RVO 00023728 Ministerstvo Zdravotnictví Ceské Republiky
RVO 00023728 Ministerstvo Zdravotnictví Ceské Republiky
RVO 00023728 Ministerstvo Zdravotnictví Ceské Republiky
RVO 00023728 Ministerstvo Zdravotnictví Ceské Republiky
NU21-05-00276 Ministerstvo Zdravotnictví Ceské Republiky
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic
SVV 260523 Ministry of Education Youth and Sports of the Czech Republic

INTRODUCTION: IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity. METHODS: Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro. RESULTS: IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes. CONCLUSION: This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.

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$a INTRODUCTION: IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity. METHODS: Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro. RESULTS: IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes. CONCLUSION: This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.
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