Zheng Liujie, Han Zhiwei, Luo Dasheng, Li Jiale, Ye Houlong, Feng Ru, Zhong Qigang, Jing Juehua, Yao Yunfeng
Department of Orthopaedic Surgery, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
Haemophilia. 2022 Nov;28(6):1062-1068. doi: 10.1111/hae.14623. Epub 2022 Jul 8.
Clarifying the links between iron and FGF23, SOX9 expression in chondrocytes would be helpful for comprehending articular cartilage degradation pathogenesis in blood-induced arthritis and exploring new protective methods.
The purpose of this study was to determine iron regulation of fibroblast growth factor 23 (FGF23) and SRY-box 9 (SOX9) in human chondrocytes, an area which is unexplored in blood-induced arthritis cartilage degradation pathogenesis.
Expression of FGF23, SOX9, MMP13 and collagen Ⅱ in articular cartilage of patients with osteoarthritis (OA) or haemophilic arthritis (HA) was determined by western blot (WB). Iron-induced FGF23 and SOX9 mRNA and protein expression in primary human normal chondrocyte cells (HUM-iCell-s018) was quantified by qRT-PCR and WB, respectively.
We found that compared with OA patients, the expression of FGF23, MMP13 in articular cartilage of patients with HA was up-regulated, while the expression of SOX9, collagen Ⅱ was down-regulated. Iron-induced FGF23 and suppressed SOX9 expression in chondrocytes in a dose-dependent manner.
These findings demonstrated that iron was involved in hemophilic cartilage lesion directly via changing cartilage phenotype through regulation of FGF23 and SOX9 expression in chondrocytes.
阐明铁与成纤维细胞生长因子23(FGF23)、软骨细胞中SOX9表达之间的联系,将有助于理解血液性关节炎中关节软骨降解的发病机制,并探索新的保护方法。
本研究的目的是确定铁对人软骨细胞中成纤维细胞生长因子23(FGF23)和SRY盒9(SOX9)的调节作用,这是血液性关节炎软骨降解发病机制中尚未探索的领域。
采用蛋白质免疫印迹法(WB)检测骨关节炎(OA)或血友病性关节炎(HA)患者关节软骨中FGF23、SOX9、基质金属蛋白酶13(MMP13)和Ⅱ型胶原蛋白的表达。分别通过实时定量聚合酶链反应(qRT-PCR)和WB定量检测铁诱导的原代人正常软骨细胞(HUM-iCell-s018)中FGF23和SOX9的mRNA及蛋白表达。
我们发现,与OA患者相比,HA患者关节软骨中FGF23、MMP13的表达上调,而SOX9、Ⅱ型胶原蛋白的表达下调。铁以剂量依赖的方式诱导软骨细胞中FGF23表达并抑制SOX9表达。
这些发现表明,铁通过调节软骨细胞中FGF23和SOX9的表达来改变软骨表型,从而直接参与血友病性软骨损伤。