Experimental Gerontology ( IF 3.9 ) Pub Date : 2023-03-15 , DOI: 10.1016/j.exger.2023.112140 Guang Xia 1 , Zi Wen 1 , Lina Zhang 1 , Junjie Huang 2 , Xinxing Wang 1 , Chi Liang 1 , Xiaoyu Cui 3 , Xu Cao 2 , Song Wu 1
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.
中文翻译:
β-羟基丁酸通过 hnRNP A1 介导的 PTEN 上调减轻软骨衰老
衰老软骨细胞在骨关节炎 (OA) 进展中起重要作用。然而,通过干预衰老的软骨细胞来缓解 OA 进展仍然面临巨大挑战。β-羟基丁酸酯 (BHB) 在多种与年龄相关的疾病中表现出抗衰老作用,但其在骨关节炎中的作用仍知之甚少。为了探索分子机制,基因测序被用来识别关键基因和潜在的细胞信号通路,雄性 SD 大鼠被用来生成骨关节炎模型。结果表明,BHB 可减轻骨关节炎软骨细胞 (OA-Chos) 的衰老并缓解 OA 进展。基因本体论 (GO) 富集分析揭示了细胞周期基因的显着变化,其中 PTEN 是最显着的差异表达基因。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 hnRNP A1 结合并抑制 Akt 的磷酸化来促进 PTEN 的表达。该研究提供了 BHB 减轻软骨细胞衰老和延迟 OA 的证据,因此可以用作骨关节炎治疗的新治疗方法。