The effects of cobalt and chromium ions on transforming growth factor‐beta patterns and mineralization in human osteoblast‐like MG63 and SaOs‐2 cells

Abstract

Bone homeostasis, the balance of bone formation and resorption is affected by numerous influences, such as, hormones, inflammation, mechanical load, and external stimuli. The transforming growth factor-beta (TGF-β), which exists in three isoforms in humans, is a major factor in the maintenance of this balance by regulating osteoblast and osteoclast maturation, development, and function. In artificial joint replacements, release of particles or ions from arthroplasties may exert local effects on the periprosthetic tissue and modulate the expression of bone specific genes and functions. Therefore, the influence of cobalt (II) and chromium (III) ions on the expression levels of the three TGF-β isoforms in human osteosarcoma cell lines MG63 and SaOs-2 was analyzed and the impact on mineralization was studied. The osteosarcoma cell lines expressed all three TGF-β isoforms, with TGF-β1 being the most abundant isoform. A dose dependent reduction of all TGF-β isoforms by Co ions was observed, the strongest effect was found on TGF-β2. The effect was lesser pronounced in SaOs-2 cells. However, the Cr ions had no significant effect on the expression of all TGF-β isoforms. In contrast, Co ions in a concentration range of 50-250 µM did not impair the mineralization, but Cr exerted a strong inhibitory effect on the mineralization in a dose dependent fashion. These data suggest that the influence of cobalt ions on bone homeostasis may in part result from the inhibitory effect on the transcription of the bone regulating cytokines TGF-β1-3 whereas the chromium ions affect the process of mineralization. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2105-2115, 2018.

Differential Effect of Cobalt and Chromium Ions as Well as CoCr Particles on the Expression of Osteogenic Markers and Osteoblast Function

“…One reason for this effect could be changes in proliferation or metabolic activity. As shown previously the metabolic activity was slightly up-regulated by Co 2+ , whereas Cr 3+ exhibited no effects on the cell metabolisms measured by water soluble tetrazolium (WST)-1 test [ 23 ]. Since metabolic activity determined using the WST-1 assay cannot be equated with proliferation, the proliferative activity of MG63 and SaOs-2 cells was measured after 48 h by determination of DNA replication using the BrdU assay—the results are similar to those of the WST-1 data, as well as the quantitative RT-PCR for the proliferation marker PCNA.…”

“…While Co 2+ down-regulated the expression of all three TGF-β isoforms in osteoblast-like cells, no inhibitory effect on mineralization was seen in the tested concentrations. Cr 3+ , however, did not influence the expression of TGF-β but strongly inhibited the mineralization in vitro [ 23 ]. These data suggest that the influence of Co 2+ ions on bone homeostasis may be related to the inhibitory effect on the transcription of the bone formation regulating cytokines e.g., TGF-β1-3 and thereby on the bone forming activity of osteoblasts e.g., collagen production.…”

“…Shah et al showed comparable effects of cobalt and chromium on the mineralization of murine “osteoblast to osteocyte-like” cell line MLO-A5 [ 37 ]. The inhibition of mineralization by soluble Cr 3+ or on soluble CrPO 4 might be due to the binding of phosphate to Cr 3+ , thereby reducing the availability of the ionic form [ 23 ]. However, this interaction needs to be analyzed in further studies.…”

“…Alrabeah and co-workers demonstrated that Co 2+ metal ions in the culture media induced the production of pro-inflammatory cytokines in human osteoblastic cells, thereby inducing a shift of bone homeostasis towards bone resorption [ 22 ]. Furthermore, it is known that Co 2+ ions reduce the expression of all three TGF-β isoforms in osteosarcoma cell lines MG63 and SaOs-2 in a dose-dependent manner, with the strongest impact on TGF-β2 resulting in a change of the TGF-β isoform pattern [ 23 ]. It is still unknown whether these changes in the expression pattern of TGF-β isoforms are involved in the dysregulation of the periprosthetic bone metabolism and function of osteoblasts.…”

In vivo corrosion and damages in modular shoulder prostheses

“…RLLs are an indicator for bone loss, most likely by osteonecrotic processes (Boileau et al, ). Several studies link an increased heavy metal ion concentration to adverse biological reactions in periprosthetic tissue, system effects (Drynda et al, ; Hallab et al, ; Khair, Nam, DiCarlo, & Su, ) as well as an induction of osteonecrosis (Andrews, Shah, Wilkinson, & Gartland, ; Klutzny et al, ). Therefore, our findings might indicate a link between the increased corrosion susceptibility of CoCrMo cast alloy with the significant occurrence of a RLL near the taper junction.…”