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IL‐9 exhibits elevated expression in osteonecrosis of femoral head patients and promotes cartilage degradation through activation of JAK‐STAT signaling in vitro

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ABSTRACT Osteonecrosis of the femoral head (ONFH) often causes severe symptoms in young people and limits the mobility of the hip joint. Interleukin‐9 (IL‐9) is a multi‐functional inflammatory factor that… Click to show full abstract

ABSTRACT Osteonecrosis of the femoral head (ONFH) often causes severe symptoms in young people and limits the mobility of the hip joint. Interleukin‐9 (IL‐9) is a multi‐functional inflammatory factor that participates in lumbar disk herniation and arthritis and has been reported in many studies. However, the correlation between IL‐9 and ONFH is unclear. The present study aimed to determine the role of IL‐9 in the pathogenetic mechanism of osteonecrosis. To assess IL‐9 expression in ONFH and femoral neck fracture patients, cartilage tissue was examined through western blot analysis and immunohistochemistry. Human primary chondrocytes were stimulated with IL‐9, and inflammation‐related cytokines and cartilage matrix‐degrading enzymes were assessed via real‐time PCR. After being treated with IL‐9, Janus kinase‐signal transducers and activators of transcription (JAK‐STAT) signaling were tested through western blot analysis. Our results showed a significant increase in the expression of IL‐9 in ONFH patients. IL‐9 raised the level of inflammation‐related cytokines and cartilage matrix‐degrading enzymes and enhanced the activation of JAK‐STAT signaling. Furthermore, blocking the JAK‐STAT signaling pathway reduced the secretion of inflammation‐related cytokines and cartilage matrix‐degrading enzymes and markedly alleviated the degradation of the cartilage matrix. These findings provide new insights into the role that IL‐9 plays in the pathogenetic mechanism of osteonecrosis and also provide a potential treatment for ONFH. HIGHLIGHTSInflammation cytokines participate in the progression of the ONFH.In the ONFH patients, the expression of IL‐9 increased in serum and cartilage samples.IL‐9 raised the level of inflammation‐related cytokines and cartilage matrix‐degrading enzymes.Inhibitor of JAK‐STAT attenuates IL‐9 induced inflammation reaction and cartilage catabolism.

Keywords: osteonecrosis; stat signaling; cartilage; jak stat

Journal Title: International Immunopharmacology
Year Published: 2018

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