Open AccessPhgdh serves a protective role in Il‑1β induced chondrocyte inflammation and oxidative‑stress damage
Author(s) -
Huang Hu,
Keting Liu,
Hua Ou,
Xuankun Qian,
JianShan Wan
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.12058
Subject(s) - oxidative stress , inflammation , chondrocyte , superoxide dismutase , apoptosis , microbiology and biotechnology , reactive oxygen species , matrix metalloproteinase , biology , chemistry , in vitro , biochemistry , immunology
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 in vivo and in vitro . Additionally, the role of Phgdh in extracellular matrix (ECM) synthesis, inflammation, apoptosis and oxidative stress levels of chondrocytes was detected in vitro . 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.