铁通过 PTEN/PI3 K/AKT/FOXO1 通路调节血友病性软骨中成软骨细胞表型。

Iron regulates chondrocyte phenotype in haemophilic cartilage through the PTEN/PI3 K/AKT/FOXO1 pathway.

机构信息

Department of Orthopaedic Surgery, The Fourth Hospital of Wuhan, Wuhan, People's Republic of China.

Department of Orthopaedic Surgery, The Second Hospital of Anhui Medical University, Hefei, People's Republic of China.

出版信息

Hematology. 2023 Dec;28(1):2240585. doi: 10.1080/16078454.2023.2240585.

DOI:10.1080/16078454.2023.2240585

PMID:37493406

Abstract

OBJECTIVE

Our previous study demonstrated that iron overload could lead to haemophilic cartilage destruction by changing chondrocyte phenotype. This change was caused by iron's effect on chondrocyte expression of FGF23 and SOX9, in addition to iron-induced chondrocyte apoptosis and cartilage extracellular matrix degradation. However, the underlying mechanisms remain unclear. This study aimed to determine the mechanism by which iron influences chondrocyte phenotype in the pathogenesis of haemophilic cartilage destruction.

METHODS

The expression of the PTEN/PI3K/AKT/FOXO1 signal pathway in the articular cartilage of patients with haemophilic arthritis (HA) or osteoarthritis (OA) was determined using western blot (WB). Additionally, we quantified the expression of iron-induced PTEN, PI3K, p-PI3K, AKT, p-AKT, FOXO1, and p-FOXO1 in primary human normal chondrocyte cells (HUM-iCell-s018) using WB.

RESULTS

We found that compared to that in patients with OA, the expression of PTEN, PI3K, AKT, and FOXO1 in the articular cartilage of patients with HA was up-regulated, while the expression of p-PI3K, p-AKT, and p-FOXO1 was down-regulated. Additionally, iron increased the expression of PTEN, PI3K, AKT, and FOXO1 and suppressed that of p-PI3K, p-AKT, and p-FOXO1 in chondrocytes in a dose-dependent manner.

CONCLUSIONS

Our findings demonstrated that iron was involved in the pathogenesis of haemophilic cartilage destruction by affecting chondrocyte phenotype through the inhibition of the PTEN/PI3K/AKT/FOXO1 pathway.

摘要

目的

我们之前的研究表明，铁过载通过改变软骨细胞表型导致血友病性软骨破坏。这种变化是由铁对软骨细胞 FGF23 和 SOX9 表达的影响以及铁诱导的软骨细胞凋亡和软骨细胞外基质降解引起的。然而，其潜在机制尚不清楚。本研究旨在确定铁在血友病性软骨破坏发病机制中影响软骨细胞表型的机制。

方法

通过 Western blot（WB）检测血友病性关节炎（HA）或骨关节炎（OA）患者关节软骨中 PTEN/PI3K/AKT/FOXO1 信号通路的表达。此外，我们通过 WB 定量检测了铁诱导的原代人正常软骨细胞（HUM-iCell-s018）中 PTEN、PI3K、p-PI3K、AKT、p-AKT、FOXO1 和 p-FOXO1 的表达。

结果

与 OA 患者相比，HA 患者关节软骨中 PTEN、PI3K、AKT 和 FOXO1 的表达上调，而 p-PI3K、p-AKT 和 p-FOXO1 的表达下调。此外，铁以剂量依赖的方式增加软骨细胞中 PTEN、PI3K、AKT 和 FOXO1 的表达，并抑制 p-PI3K、p-AKT 和 p-FOXO1 的表达。