Bergamot Polyphenol Fraction Exerts Effects on Bone Biology by Activating ERK 1/2 and Wnt/β-Catenin Pathway and Regulating Bone Biomarkers in Bone Cell Cultures

Arturo Pujia; Cristina Russo; Samantha Maurotti; Roberta Pujia; Vincenzo Mollace; Stefano Romeo; Tiziana Montalcini

doi:10.3390/nu10091305

Bergamot Polyphenol Fraction Exerts Effects on Bone Biology by Activating ERK 1/2 and Wnt/β-Catenin Pathway and Regulating Bone Biomarkers in Bone Cell Cultures

Nutrients. 2018 Sep 14;10(9):1305. doi: 10.3390/nu10091305.

Authors

Arturo Pujia¹, Cristina Russo², Samantha Maurotti³, Roberta Pujia⁴, Vincenzo Mollace⁵, Stefano Romeo^{6

7}, Tiziana Montalcini⁸

Affiliations

¹ Department of Medical and Surgical Science, University Magna Grecia, 88100 Catanzaro, Italy. [email protected].
² Department of Medical and Surgical Science, University Magna Grecia, 88100 Catanzaro, Italy. [email protected].
³ Department of Medical and Surgical Science, University Magna Grecia, 88100 Catanzaro, Italy. [email protected].
⁴ Department of Health Science, University Magna Grecia, 88100 Catanzaro, Italy. [email protected].
⁵ Department of Health Science, University Magna Grecia, 88100 Catanzaro, Italy. [email protected].
⁶ Department of Medical and Surgical Science, University Magna Grecia, 88100 Catanzaro, Italy. [email protected].
⁷ Department of Molecular and Clinical Medicine, University of Gothenburg, 40530 Gothenburg, Sweden. [email protected].
⁸ Department of Clinical and Experimental Medicine, Nutrition Unit, University Magna Grecia, 88100 Catanzaro, Italy. [email protected].

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.

Keywords: Bergamot; Saos-2; bone cells; citrus fruits; osteoporosis; polyphenols; β-catenin.

MeSH terms

Biomarkers / metabolism
Bone Remodeling / drug effects*
Cell Differentiation / drug effects
Cell Line
Citrus* / chemistry
Collagen Type I / genetics
Collagen Type I / metabolism
Core Binding Factor Alpha 1 Subunit / genetics
Core Binding Factor Alpha 1 Subunit / metabolism
Enzyme Activation
Fruit
Humans
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Osteoblasts / drug effects*
Osteoblasts / enzymology
Phosphorylation
Plant Extracts / isolation & purification
Plant Extracts / pharmacology*
Polyphenols / isolation & purification
Polyphenols / pharmacology*
RANK Ligand / genetics
RANK Ligand / metabolism
Wnt Signaling Pathway / drug effects*
beta Catenin / genetics
beta Catenin / metabolism

Substances

Biomarkers
CTNNB1 protein, human
Collagen Type I
Core Binding Factor Alpha 1 Subunit
Plant Extracts
Polyphenols
RANK Ligand
RUNX2 protein, human
TNFSF11 protein, human
beta Catenin
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3