Abstract

Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1α), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 μM. Cell viability, HIF-1α protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from different sources, in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies.

Highlights

  • Hyaline articular cartilage has a very limited or no intrinsic capacity for repair and minor traumatic lesions or pathological injuries may trigger progressive damage and joint degeneration [1]

  • The microenvironment of mesenchymal stromal cells (MSCs) is characterized by a low oxygen tension, demonstrating that MSCs might be quite resistant to oxygen limitation [11]

  • The transcription factor hypoxia-inducible factor- (HIF)-1 is composed of two subunits, HIF-1α and HIF-β or aryl hydrocarbon receptor nuclear translocator (ARNT) [14]

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Summary

Introduction

Hyaline articular cartilage has a very limited or no intrinsic capacity for repair and minor traumatic lesions or pathological injuries may trigger progressive damage and joint degeneration [1]. Novel cell-based tissue engineering techniques have been proposed with the aim to repair cartilage defects and reconstitute the properties of hyaline cartilage. The key adaptive response to hypoxic conditions is the stabilization of hypoxia-inducible factor- (HIF) 1 [13]. The transcription factor HIF-1 is composed of two subunits, HIF-1α and HIF-β or aryl hydrocarbon receptor nuclear translocator (ARNT) [14]. In both normoxic and hypoxic conditions, the HIF-β is constantly biosynthesised, degraded, and recycled [15].

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