Transcriptomic comparison of the infrapatellar fat pad between young patients with traumatic knee injury and older patients with knee osteoarthritis.

PURPOSE: The infrapatellar fat pad (IFP) is increasingly recognized as an active contributor to knee osteoarthritis (KOA) pathogenesis. However, age-related transcriptional changes in the IFP remain poorly understood, and whether observed differences are purely age-dependent or confounded by disease status is unclear. This study aimed to compare transcriptomic profiles of the IFP between young patients with traumatic knee injury and older patients with KOA. METHODS: IFP samples were obtained from three young trauma patients (21-28 years, KL grade 0) and three older patients with KOA (64-72 years, KL grade III-IV). Bulk RNA sequencing was performed to compare transcriptomes between groups. Differential expression was analyzed with DESeq2 (|log2FC| ≥1, unadjusted p < 0.05), followed by GO and KEGG pathway enrichment. Real-time PCR confirmed key expression changes. RESULTS: Compared with the young trauma group, the old KOA group exhibited 247 upregulated (CSN1S1, SCN9A, P2RY14, EIF3C, etc) and 334 downregulated genes (PI15, WISP3, DMKN, NUTM2G, etc). The old KOA group exhibited significantly reduced expression of extracellular matrix (ECM) genes, including COL1A1, COL2A1, and FN1. Additionally, core genes of the PI3K-Akt signaling pathway, such as AKT1, ITGA2B, and MYB, were also downregulated in the old KOA group. CONCLUSIONS: The IFP in old KOA exhibits a transcriptomic profile characterized by dampened ECM structural gene expression and suppressed PI3K-Akt signaling compared with young trauma patients. While confounded by injury status, these findings suggest that age-related loss of ECM integrity may contribute to IFP dysfunction in established KOA and warrant validation in healthy aging cohorts.