Department of Orthopaedics, Qujing First People's Hospital, Qujing, Yunnan 655000, P.R. China.
Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12058. Epub 2021 Apr 13.
The primary pathological changes observed in osteoarthritis (OA) involve inflammation and degeneration of chondrocytes. 3‑phosphoglycerate dehydrogenase (Phgdh), a rate‑limiting enzyme involved in the conversion of 3‑phosphoglycerate to serine, serves as a crucial molecular component of cell growth and metabolism. However, its effects on chondrocytes in OA have not been determined. In the present study, a rat model of OA was used to investigate the expression levels of Phgdh and . Additionally, the role of Phgdh in extracellular matrix (ECM) synthesis, inflammation, apoptosis and oxidative stress levels of chondrocytes was detected . Phgdh expression was decreased in OA, and Phgdh overexpression promoted ECM synthesis, decreased levels inflammatory cytokines, such as Il‑6, TNF‑α, a disintegrin and metalloproteinase with thrombospondin motifs 5 and MMP13, and decreased apoptosis. Furthermore, expression of Phgdh effectively increased expression levels of the cellular antioxidant enzymes catalase and superoxide dismutase 1, and decreased the levels of reactive oxygen species in chondrocytes; and this may have been regulated by a Kelch like ECH associated protein 1/nuclear factor erythroid 2‑related factor 2 axis. Taken together, these results suggest that Phgdh may be used to manage the progression of OA.
在骨关节炎（OA）中观察到的主要病理变化涉及软骨细胞的炎症和变性。3-磷酸甘油酸脱氢酶（Phgdh）是参与 3-磷酸甘油酸转化为丝氨酸的限速酶，是细胞生长和代谢的重要分子组成部分。然而，其在 OA 中的软骨细胞中的作用尚未确定。在本研究中，使用 OA 大鼠模型来研究 Phgdh 和 的表达水平。此外，还检测了 Phgdh 在软骨细胞的细胞外基质（ECM）合成、炎症、凋亡和氧化应激水平中的作用。OA 中 Phgdh 的表达降低，Phgdh 过表达促进 ECM 合成，降低白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、解整合素金属蛋白酶 13（ADAMTS13）和基质金属蛋白酶 13（MMP13）等炎症细胞因子的水平，并减少凋亡。此外，Phgdh 的表达有效增加了细胞抗氧化酶过氧化氢酶和超氧化物歧化酶 1 的表达水平，并降低了软骨细胞中的活性氧水平；这可能通过 Kelch 样 ECH 相关蛋白 1/核因子红细胞 2 相关因子 2 轴进行调节。综上所述，这些结果表明 Phgdh 可用于管理 OA 的进展。
