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Phgdh serves a protective role in Il‑1β induced chondrocyte inflammation and oxidative‑stress damage

Hefei Huang1, Keting Liu1, Hua Ou1

  • 1Department of Orthopaedics, Qujing First People's Hospital, Qujing, Yunnan 655000, P.R. China.

Molecular Medicine Reports
|April 13, 2021
PubMed

Insights

3‑phosphoglycerate dehydrogenase (Phgdh) is reduced in osteoarthritis (OA). Overexpressing Phgdh in chondrocytes protects against OA by promoting extracellular matrix synthesis and reducing inflammation, apoptosis, and oxidative stress.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pathology

Background:

  • Osteoarthritis (OA) is characterized by chondrocyte inflammation and degeneration.
  • 3‑phosphoglycerate dehydrogenase (Phgdh) is a key enzyme in serine synthesis, vital for cell growth and metabolism.
  • The role of Phgdh in OA chondrocytes remains largely undetermined.

Purpose of the Study:

  • To investigate Phgdh expression levels in an OA rat model (in vivo and in vitro).
  • To determine the function of Phgdh in chondrocyte extracellular matrix (ECM) synthesis, inflammation, apoptosis, and oxidative stress.
  • To explore the regulatory mechanism of Phgdh in chondrocytes.

Main Methods:

  • Utilized a rat model of osteoarthritis to assess Phgdh expression.
  • Conducted in vitro experiments to evaluate Phgdh's impact on chondrocyte ECM synthesis, inflammatory markers, apoptosis, and oxidative stress.
  • Investigated the role of the Keap1/Nrf2 pathway in Phgdh-mediated effects.

Main Results:

  • Phgdh expression was found to be decreased in OA.
  • Overexpression of Phgdh enhanced ECM synthesis and upregulated antioxidant enzymes (catalase, SOD1).
  • Phgdh overexpression reduced inflammatory cytokines (IL-6, TNF-α, ADAMTS5, MMP13), apoptosis, and reactive oxygen species (ROS).

Conclusions:

  • Phgdh expression is diminished in osteoarthritis.
  • Phgdh plays a protective role in chondrocytes by mitigating inflammation, apoptosis, and oxidative stress.
  • Phgdh, potentially regulated by the Keap1/Nrf2 axis, shows therapeutic potential for managing OA progression.

Keywords:
Phgdhchondrocytesinflammationoxidative stressosteoarthritis

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