Paradoxical effects of hypoxia-mimicking divalent cobalt ions in human endothelial cells in vitro

Abstract

Divalent cobalt ions (Co2+) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro study we compared the effects of hypoxia and Co2+ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) under different hypoxic conditions (3% and nearly 0% O2) and Co2+ -concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1alpha protein was enhanced by exposure to Co2+ (did not correlate with mRNA amount). however, contrary to the results of hypoxia, in vitro-angiogenesis was inhibited after exposure to even low Co2+-concentrations (> or =0.01 mM). This led to the conclusion that although hypoxia signaling after Co2+ -exposure took place, further yet unknown Co2+ -induced event(s) must have occurred.

Hypoxia-mimicking bioactive glass regenerative effects on dental stem cells

“…In contrast to DPSC, no differences were seen after exposure of SHED to the 1Co BG or to the 0Co BG or CTL conditions. This suggested that cobalt ions may trigger different responses depending of the source of dental stem cells, as previously demonstrated in other cell types such as periodontal cells [17], endothelial cells [11], and bone marrow stem cells [16]. While cobalt-containing BG have the potential to stimulate the release of angiogenic growth factors in DPSC, and may benefit dental repair when associated with such cell types, further investigations would be needed to better understand how different dental progenitor cell types are influenced by cobalt.…”

“…This concentration appeared suitable to induce cobaltdependent cellular responses, e.g. HIF-1 pathway activation and VEGF expression [11]. …”

“…Cobalt ions have been shown to promote the production and release of VEGF from various cell types [12,13] whether the ions were delivered from the dissolution of salts, such as cobalt chloride [11,14], or released from bioactive glasses [15,16]. It has been shown in hMSC that this process was due to the capacity of the cobalt ions released from BG to activate the HIF-1 pathway [15].…”

CoCrMo alloy treated by floating potential plasma assisted nitriding and plasma based ion implantation: Influence of the hydrogen content and of the ion energy on the nitrogen incorporation

“…However, when coupling different solicitations (as wear or fretting and corrosion), the protective passive layer of chromium oxide is no more sufficient to protect it from catastrophic wear and release of metallic (nano-) particles in the body [3]. They may then act as wear third body, leading to a more pronounced degradation of the metallic prosthesis or its UHMWPE counterpart, or poison the human body fluid, leading to various cell necrosis [4,5].…”

Destructive and Non-Destructive Properties of Cobalt Oxide Substituted 1393 Bioactive Glass

“…27 1393 bioactive glasses tolerate strong bonding to hard and soft tissue and have been shown to endorse osteogenesis via the activation of several relevant genes. 28 Cobalt ions are considered important in bone physiology [29][30][31][32] as they induce hypoxia conditions and become stable hypoxia-inducible factor 33,34 which in turn, activates several pro-regenerative processes in the human body. 35 HIF-1 activation leads to angiogenesis, stem cell differentiation, and fracture repair.…”