Abstract

Bone mass loss occurs with a decrease in osteoblast proliferation and differentiation, or the enhancement of bone resorption, which further leads to the impairment of bone mineral density and increase in bone fracture. Recent studies suggest that some phenolic compounds found in food play positive role in bone metabolism. High content of phenolic compounds with potential beneficial effects on bone metabolism have been identified in the Viburnum opulus fruit. The aim of the study was to determine the influence of V. opulus fresh juice (FJ) and juice purified by solid phase extraction (PJ) on osteogenesis processes with osteosarcoma Saos-2 cell lines. V. opulus purified juice revealed stronger potential as an inducer of Saos-2 osteogenic differentiation. Saos-2 cells matrix mineralization was evaluated with alkaline phosphatase (ALP) activity measurement and alizarin red S staining. Gene expression analysis showed the elevation of the mRNA levels of Runt-related transcription factor 2 (RUNX2), ALP, collagen type 1 and osteonectin, whereas the nuclear factor-κB ligand and osteoprotegerin ratio (RANKL/OPG) decreased. Furthermore, V. opulus was able to diminish the secretion of pro-inflammatory cytokines Il6 and TNFα, however had no effect on vascular endothelial growth factor (VEGF). It decreased intracellular oxidative stress and induced DNA repair, but had no effect on the growth inhibition of lactic acid beneficial microorganisms.

Highlights

  • Homeostasis between bone resorption and bone formation maintains bone tissue integrity and health, and is controlled both by physical stimulation and cellular signaling molecules [1,2]

  • Taking into account a significant impact of V. opulus phenolic compounds on the modulation of cellular metabolism, as well as its phenolic compounds composition, in the present study we investigated the effect of V. opulus fruit juice on the metabolic activity and mineralization process in human osteosarcoma Saos-2 cell lines

  • The fresh juice (FJ) and purified juice (PJ) showed the presence of different groups of phenolic compounds, such as hydroxycinnamic acids, flavanols, flavonols- and anthocyanins

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Summary

Introduction

Homeostasis between bone resorption and bone formation maintains bone tissue integrity and health, and is controlled both by physical stimulation and cellular signaling molecules [1,2]. The reduction in osteogenesis occurs with an enhancement of bone resorption, leading to the impairment of bone mineral density and increase in bone fractures [4]. The other mechanisms leading to osteoclast activation and maturation involve signal transduction after the receptor activator of the nuclear factor-κB ligand (RANKL) binding with its RANK receptor, expressed by osteoclasts. The osteoprotegerin (OPG) secreted by osteoblasts captures RANKL, which limits its binding to the RANK receptor and, in turn, sustains bone mass. Obesity-related enhanced adipocyte growth leads to the elevation of proinflammatory cytokine production, and intensifies osteoclast differentiation via RANKL/RANK/OPG signal transduction and, bone resorption [8,9,10,11]. In the prevention and treatment of osteoporosis, there are used estrogens or selective estrogen receptor modulators; due to the side effects resulting from their prolonged usage, less harmful plant derived substitutes are being searched [12]

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