The effect of quercetin on the antioxidant response and phenotypic development of osteoblasts

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Jonathan G. Messer (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Deborah Kipp

Abstract: Oxidative stress plays a major role in development of osteoporosis, in part, by suppressing the differentiation and function of bone forming osteoblasts. This finding suggests that strategies to prevent or reverse osteoporosis may lie in targeting the osteoblast antioxidant response. Quercetin is an antioxidant flavonoid found abundantly in the diet and in supplements, and is known to induce expression of antioxidant response genes and proteins in a variety of cell types. The purpose of these studies was to examine the extent that quercetin metabolites up-regulate the antioxidant response, to identify cell signaling pathways that might be involved, and to examine the extent that quercetin preserves development of the osteoblast phenotype when cells are cultured in an oxidative stress environment. We hypothesized that quercetin metabolites would up-regulate the antioxidant response, and that this up-regulation would protect cells from oxidative stress-induced suppression. Studies were performed in osteoblast-like cultures isolated from fetal rat calvaria that were treated with 0 to 20 µM quercetin aglycone (QRC), isorhamnetin (ISO), quercetin-3-O-glucuronide (Q3G) or a 2:1:1 mixture of all three metabolites (10 µM Q3G: 5 µM QRC: 5 µM ISO). The antioxidant response was assessed by measuring expression of antioxidant genes and proteins. Results indicated that QRC and ISO robustly up-regulated expression of two antioxidant response genes and proteins, heme oxygenase-1 (HO-1) and the catalytic subunit of gamma-glutamate cysteine ligase, but Q3G had no effect. Cell signaling protein, ERK1/2, and transcription factor NFkappaB proteins were also down-regulated by quercetin. To examine the effect of quercetin on oxidative stress-induced suppression of osteoblast phenotype, cells were pretreated 12h with 20 µM QRC followed by incubation with 0 or 300 µM hydrogen peroxide, a known inducer of oxidative stress. Differentiation was assessed by alkaline phosphatase staining and expression of osteoblast phenotypic gene markers. Pretreating cells with 20 µM QRC partially blocked hydrogen peroxide-induced suppression of osteoblast phenotype, as indicated by higher levels of alkaline phosphatase staining and gene expression of osteoblast phenotype markers compared to cells pretreated with 0 µM QRC. QRC also partially blocked hydrogen peroxide-induced up-regulation of HO-1. These results suggest that quercetin produces a low grade antioxidant response that "primes" cells to withstand a subsequent oxidative stress event, which protects development of osteoblast phenotype. These findings offer important insight into the osteoblast antioxidant stress response, and support a link between osteoblast stress signaling and phenotypic development.

Additional Information

Language: English
Date: 2014
Antioxidant response, Heme oxygenase-1, Osteoblast, Quercetin
Osteoporosis $x Prevention

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