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.

Knee osteoarthritis (KOA) is prevalent in postmenopausal women and a cause of pain and disability in elderly populations. Here, we report high follicle‐stimulating hormone (FSH) levels across postmenopausal female KOA patients aged 50–60 years. We speculate FSH might damage cartilage tissues through the phosphoinositide 3‐kinase/AKT/nuclear factor kappa B pathway. Our findings suggest that FSH modulation holds promise as a novel treatment for postmenopausal female KOA patients aged 50–60 years.

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