Follicle-stimulating hormone worsens osteoarthritis by causing inflammation and chondrocyte dedifferentiation.
Follicle-stimulating hormone worsens osteoarthritis by causing inflammation and chondrocyte dedifferentiation.
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DOI：
10.1002/2211-5463.13238
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发表时间：
2021-08
期刊：
影响因子：
2.6
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Huan Z;Wang Y;Zhang M;Zhang X;Liu Y;Kong L;Xu J
以往的研究发现，软骨细胞（软骨细胞）上存在促卵泡激素（FSH）受体，但FSH作用于软骨细胞的机制尚不清楚。本实验的目的是研究FSH是否影响软骨细胞以及它如何引起这些细胞的变化。我们的研究结果表明，在小鼠膝关节注射FSH后，骨关节炎变得更糟。在FSH刺激软骨细胞后，通过转录组学共筛选出664个上调基因，如Col 12 a1和Col 1a 1，以及644个下调基因，如MGP。对细胞外基质（ECM）相关基因和通路的一个子集进行了基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析，证实了MGP的下调、EGFR 1和Col 1a 1的上调以及IL-6的增加。FSH可抑制cAMP/PKA和MKK 4/JNK信号通路。总之，我们证明FSH可以通过抑制cAMP/PKA和MKK 4/JNK信号通路增加软骨炎症反应并促进软骨细胞去分化。在此，我们通过体内实验、转录组学筛选和体外实验证明，FSH可以抑制cAMP/PKA和MKK 4/JNK信号通路，引起炎症反应和软骨细胞去分化，从而加重骨关节炎。
Previous studies have found follicle‐stimulating hormone (FSH) receptors on chondrocytes (cartilage cells), but the mechanism of FSH action on chondrocytes is not clear. The purpose of this experiment is to study whether FSH affects chondrocytes and how it causes changes in these cells. Our results show that osteoarthritis became worse after FSH injection in the knee joint of mice. After the stimulation of chondrocytes by FSH, a total of 664 up‐regulated genes, such as Col12a1 and Col1a1, and 644 down‐regulated genes, such as MGP, were screened by transcriptomics. A subset of extracellular matrix (ECM)‐related genes and pathways underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the downregulation of MGP, the upregulation of EGR1 and Col1a1, and the increase of IL‐6 were verified. It was also observed that FSH can inhibit the cAMP/PKA and MKK4/JNK signaling pathway. In conclusion, we demonstrated that FSH can increase cartilage inflammatory response and promote chondrocyte dedifferentiation by inhibiting the cAMP/PKA and MKK4/JNK signaling pathways. Here, we demonstrate through in vivo experiments, transcriptomic screening, and in vitro experiments that FSH can inhibit cAMP/PKA and MKK4/JNK signaling pathways and cause inflammatory response and dedifferentiation of chondrocytes, thereby aggravating osteoarthritis.
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