Abstract：
Senescence chondrocytes play an important role in Osteoarthritis (OA) progression. However, alleviating OA progression through senescent chondrocyte intervention still faces great challenges. β-Hydroxybutyrate (BHB) exhibits anti-senescence effects in a variety of age-related dis-eases, but its role in osteoarthritis remains poorly understood. To explore the molecular mechanisms, gene sequencing was used to identify critical genes and potential cellular signaling pathways and male SD rats were used to generate an osteoarthritis model. Results showed that BHB attenuated the senescence of Osteoarthritis chondrocytes (OA-Chos) and alleviated OA progression. Gene ontology (GO) enrichment analysis revealed significant changes in cell cycle genes, with PTEN being the most significant differentially expressed gene. BHB up-regulated the expression of PTEN in OA-Chos, thereby alleviating chondrocyte senescence. Furthermore, BHB facilitated the expression of PTEN by binding to hnRNP A1 and inhibiting the phosphorylation of Akt. This study provided evidence that BHB mitigated chondrocyte senescence and delayed OA, and could thus be used as a novel therapeutic approach for osteoarthritis treatment.
摘要：
衰老软骨细胞在骨关节炎（OA）的发展中起重要作用。然而,通过衰老软骨细胞干预缓解OA进展仍面临巨大挑战。β-羟基丁酸酯（BHB）在各种与年龄相关的疾病中表现出抗衰老作用，但它在骨关节炎中的作用仍然知之甚少。探索分子机制，基因测序用于鉴定关键基因和潜在的细胞信号通路,雄性SD大鼠用于制备骨关节炎模型.结果表明，BHB可以减轻骨关节炎软骨细胞（OA-Chos）的衰老并减轻OA的进展。基因本体论（GO）富集分析揭示了细胞周期基因的显著变化，PTEN是最显著的差异表达基因。BHB上调OA-Chos中PTEN的表达,从而减轻软骨细胞衰老。此外，BHB通过与hnRNPA1结合并抑制Akt的磷酸化来促进PTEN的表达。这项研究提供了证据，表明BHB减轻了软骨细胞衰老和延迟性OA，因此可以作为骨关节炎治疗的一种新的治疗方法。
