Abstract

Epidemiological studies show that fruit consumption may modulate bone mineral density. However, data regarding the effect of the Citrus bergamia Risso (Bergamot orange), a citrus fruit containing a high concentration of flavonoids, on bone health are still lacking. In this study, we investigated the effects of Bergamot polyphenols on the Wnt/β-catenin pathway in two distinct bone cell types (Saos-2 and MG63). Findings showed that exposure to 0.01 and 0.1 mg/mL doses upregulate β-catenin expression (p = 0.001), osteoblast differentiation markers (e.g., RUNX2 and COL1A), and downregulate RANKL (p = 0.028), as compared to the control. Our results highlight, for the first time, that Bergamot polyphenols act on bone cells through the β-catenin pathway. In vivo studies are necessary to fully understand Bergamot’s role against bone resorption.

Highlights

  • Despite the wide range of pharmacological agents that reduce fracture risks [1,2,3,4,5,6,7,8], safety concerns have arisen regarding long-term osteoporosis pharmacotherapy

  • To test the hypothesis that Bergamot polyphenol fraction (BPF) increases osteoblast proliferation, Saos-2 cells were incubated with different doses of BPF for 24 h and cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay

  • This study, which is the first to directly investigate the effects of Bergamot polyphenols in bone models, shows that β-catenin, ERK 1/2, RUNX2, and intracellular Type 1A collagen (COL1A) proteins are upregulated by cell models, shows that β-catenin, ERK 1/2, RUNX2, and intracellular COL1A proteins are exposure to increasing doses of BPF

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Summary

Introduction

Despite the wide range of pharmacological agents that reduce fracture risks [1,2,3,4,5,6,7,8], safety concerns have arisen regarding long-term osteoporosis pharmacotherapy. The long-term use of bisphosphonates is associated with an increased risk of atypical fractures [9], upper gastrointestinal adverse events [10], and osteonecrosis of the jaw (ONJ) [11]. The use of hormone therapy (HT) for the prevention of osteoporosis in elderly postmenopausal women is currently under review, due to the increased risk of breast cancer and thromboembolic disease [13,14]. There is general consensus that the benefits of treatment far outweigh any risks associated with long-term treatment [17], but it is evident that there is an urgent need to find new and cost-efficient ways to prevent the development of osteoporosis

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