Abstract

Diets rich in fruits and vegetables with many antioxidants can be very important in the prevention and treatment of osteoporosis. Studies show that oxidative stress, often due to lack of antioxidants, is involved in alteration of bone remodeling and reduction in bone density. This study demonstrates in human osteoblast-like SaOS-2 cells that blueberry juice (BJ), containing 7.5 or 15 μg∙mL−1 total soluble polyphenols (TSP), is able to prevent the inhibition of osteogenic differentiation and the mineralization process due to oxidative stress induced by glutathione depletion. This situation mimics a metabolic condition of oxidative stress that may occur during estrogen deficiency. The effect of BJ phytochemicals occurs through redox- and non-redox-regulated mechanisms. BJ protects from oxidative damage factors related to bone remodeling and bone formation, such as alkaline phosphatase and Runt-related transcription factor 2. It upregulates these factors by activation of sirtuin type 1 deacetylase expression, a possible molecular target for anti-osteoporotic drugs. Quantitative analysis of TSP in BJ shows high levels of anthocyanins with high antioxidant capacity and bioavailability. These novel data may be important to elucidate the molecular and cellular beneficial effects of blueberry polyphenols on bone regeneration, and they suggest their use as a dietary supplement for osteoporosis prevention and therapies.

Highlights

  • Recent studies show that changes in the oxidative state and the regulation of redox homeostasis affect bone turnover and remodeling [1,2,3]

  • The data of this study demonstrate that total soluble polyphenols (TSP), together with other phytochemicals contained in blueberry juice (BJ), are able to prevent butionine sulfoximine (BSO)-induced oxidative stress, and the results partly correlate with what was previously obtained with thiol antioxidants, such as GSH and N-acetyl cysteine, in SaOS-2 cells under similar conditions of oxidative stress [13]

  • The present study demonstrated, in GSH-depleted SaOS-2 cells, that TSPs, together with other phytocompounds contained in BJ, are able to prevent early oxidative stress-induced inhibition of osteogenic differentiation and the mineralization process

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Summary

Introduction

Recent studies show that changes in the oxidative state and the regulation of redox homeostasis affect bone turnover and remodeling [1,2,3]. Excessive production of reactive oxygen species (ROS), not counterbalanced by endogenous antioxidant defense systems, induces oxidative stress with consequent abnormal osteocyte apoptosis, which activates the osteoclasts and inhibits osteoblast osteogenic activity [1,4,5,6] This is related to estrogen deficiency, aging, or bone inflammatory processes in which oxidative stress induces low bone mineral density and loss of bone mass [3,7,8,9]. Oxidative stress and a decreased reduced glutathione/oxidized glutathione (GSH/GSSG) ratio are associated with the inhibition of osteoblast differentiation and the mineralization process and alter the levels of specific osteogenic markers [13]; the ROS increase activates osteoclast differentiation [10,14]. Antioxidants counteract these negative effects and favor the activity of osteoblasts, the viability of bone stem cells, and the maintenance of a normal bone remodeling process [1,3,6,11,12,16]

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