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Hypoxia Regulates the Extracellular Matrix via Mitogen-Activated Protein Kinases Pathway in Cells Retrieved from the Human Intervertebral Disc

 Young Mi Kang  ;  Eun Jung Shin  ;  Byung Ho Lee  ;  Jae Ho Yang  ;  Hwan Mo Lee  ;  Seong Hwan Moon 
 YONSEI MEDICAL JOURNAL, Vol.62(8) : 734-742, 2021-08 
Journal Title
Issue Date
Aggrecans / genetics ; Cells, Cultured ; Extracellular Matrix ; Humans ; Hypoxia ; Intervertebral Disc* ; Mitogen-Activated Protein Kinases*
Intervertebral disc ; chondrocyte-like cell ; extracellular matrix ; low oxygen ; proteoglycan
Purpose: The present study aimed to identify the physiological characteristics of cells by investigating the change in gene expression and protein levels during extracellular matrix (ECM) synthesis in the intervertebral disc (IVD) under hypoxic conditions.

Materials and methods: To test the effect of oxygen on cell growth and ECM synthesis of chondrocyte-like cells, the cells from IVD were separated and cultured in two hypoxia-mimicking systems: chemical hypoxic conditions using deferoxamine (DFO), and physiological hypoxic conditions using a hypoxic chamber for 7 days. Chondrocyte like cells cultured without DFO and under the normal oxygen concentration (21% O₂ and 5% CO₂, 37°C) served as the controls.

Results: Chondrocyte-like cells cultured in the presence of 6% oxygen demonstrated a 100% increase in cellular proliferation compared to the control. The cells treated with chemical hypoxic conditions demonstrated a dose-dependent increase in the mRNA expression of glucose transporter-1, GAPDH, aggrecan, and type II collagen on Day 1. When treated with 100 µM DFO, the cells showed a 50% increase in the levels of proteoglycan protein on Day 7. The cells treated with chemical hypoxic condition demonstrated increase in sulfated glycosaminoglycan (GAG) protein levels on Day 7. Moreover, the cells cultured in the presence of 6% oxygen showed a 120% increase in sulfated GAG levels on Day 7.

Conclusion: The oxygen concentration had an important role in the viability, proliferation, and maturation of chondrocyte-like cells in IVD. In addition, chondrocyte-like cells are sensitive to the concentration of oxygen.
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1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Moon, Seong Hwan(문성환)
Yang, Jae Ho(양재호) ORCID logo https://orcid.org/0000-0001-7421-2805
Lee, Byung Ho(이병호) ORCID logo https://orcid.org/0000-0001-7235-4981
Lee, Hwan Mo(이환모) ORCID logo https://orcid.org/0000-0002-5405-3832
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