IL-6, IL-1β and TNF-α regulation of the chondrocyte phenotype: a possible mechanism of haemophilic cartilage destruction
Liujie Zheng,
Zhiwei Han,
Dasheng Luo,
Jiale Li,
Nanyu Pang,
Mingyang Ding,
Houlong Ye,
Keyan Zhu,
Yunfeng Yao
Affiliations
Liujie Zheng
Department of Orthopaedic Surgery, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
Zhiwei Han
Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China
Dasheng Luo
Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China
Jiale Li
Department of Orthopaedic Surgery, Fuyang Hospital of Anhui Medical University, Fuyang, People’s Republic of China
Nanyu Pang
Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China
Mingyang Ding
Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China
Houlong Ye
Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China
Keyan Zhu
Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China
Yunfeng Yao
Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of China
ABSTRACTObjective: Proinflammatory cytokines are considered to be one of the key causes of haemophilic cartilage destruction by inducing chondrocyte apoptosis and extracellular matrix degradation. However, few studies have focused on how proinflammatory cytokines regulate the phenotypic changes of chondrocytes, which may be an important factor in haemophilic cartilage degradation pathogenesis. More understanding is needed about the effect of proinflammatory cytokines on phenotypic changes of the chondrocyte. The objective of this study was to examine how IL-6, TNF-α and IL-1β regulate the chondrocyte phenotype, which may be an important factor in haemophilic cartilage degradation pathogenesis.Methods: HUM-iCell-s018 chondrocytes were treated with increasing concentrations of TNF-α, IL-6 or IL-1β (0, 1, 5, 10 ng/ml) for 24 h, then FGF23 and SOX9 expression was determined by qRT-PCR and WB, respectively.Results: We found that TNF-α, IL-6 and IL-1β induced FGF23 and suppressed SOX9 expression in chondrocytes in a dose-dependent manner. IL-1β had a stronger regulatory effect on FGF23, while TNF-α and IL-6 had stronger regulatory effects on SOX9.Conclusions: These findings suggest that IL-6, IL-1β and TNF-α may be involved in haemophilic cartilage destruction pathogenesis by altering the chondrocyte phenotype through modulation of FGF23 and SOX9 gene expression.
