Department of Traumatology, The Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Avenue, Wuhua District, Kunming, 650000, Yunnan, China.
J Mol Histol. 2023 Oct;54(5):427-438. doi: 10.1007/s10735-023-10143-8. Epub 2023 Sep 2.
Osteoarthritis (OA) is a systemic joint degenerative disease involving a variety of cytokines and growth factors. In this study, we investigated the protective effect of fibroblast growth factor 1 (FGF1) knockdown on OA and its underlying mechanisms in vitro. In addition, we evaluated the effect of FGF1 knockout on the destabilization of the medial meniscus (DMM) and examined the anterior and posterior cruciate ligament model in vivo. FGF1 affects OA cartilage destruction by increasing the protein expression of Nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), which is associated with the phosphorylation of AMPK and its substrates. Our study showed that FGF1 knockdown could reverse the oxidative damage associated with osteoarthritis. Nrf2 knockdown eliminated the antioxidant effect of FGF1 knockdown on chondrocytes. Furthermore, AMPK knockdown could stop the impact of FGF1 knockdown on osteoarthritis. These findings suggested that FGF1 knockdown could effectively prevent and reverse osteoarthritis by activating AMPK and Nrf2 in articular chondrocytes.
骨关节炎（OA）是一种全身性关节退行性疾病，涉及多种细胞因子和生长因子。在这项研究中，我们研究了成纤维细胞生长因子 1（FGF1）敲低对 OA 的保护作用及其体外的潜在机制。此外，我们还评估了 FGF1 敲除对内侧半月板不稳定（DMM）的影响，并在体内检查了前交叉韧带和后交叉韧带模型。FGF1 通过增加核因子 E2 相关因子 2（Nrf2）和血红素加氧酶 1（HO-1）的蛋白表达，影响 OA 软骨破坏，这与 AMPK 及其底物的磷酸化有关。我们的研究表明，FGF1 敲低可以逆转与骨关节炎相关的氧化损伤。Nrf2 敲低消除了 FGF1 敲低对软骨细胞的抗氧化作用。此外，AMPK 敲低可以阻止 FGF1 敲低对骨关节炎的影响。这些发现表明，FGF1 敲低通过激活关节软骨细胞中的 AMPK 和 Nrf2 可以有效预防和逆转骨关节炎。
