Zingerone stimulates osteoblast differentiation by increasing Smad1/5/9‐mediated HO‐1 expression in MC3T3‐E1 cells and primary mouse calvarial cells. (19th July 2022)

• Record Type: Journal Article
• Authors: Kim, A‐Rang; Lim, Young‐Ju; Jang, Won‐Gu
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 49:Number 10(2022)
• Page Start: 1050
• Page End: 1058
• Publication Date: 2022-07-19
• Subjects: HO‐1 -- osteoblast differentiation -- Smad1/5/9 -- zebrafish -- zingerone; Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.13681
• Languages: English
• ISSNs: 0305-1870

Abstract

Abstract: Zingerone is a non‐volatile compound found mainly in dried ginger. Zingerone increases the expression of osteogenic markers and has antioxidant effects. A previous study showed that zingerone accelerated osteoblast differentiation by suppressing the expression of Smad7, a member of the inhibitory Smad (I‐Smad) family. However, it is not known if zingerone can induce osteoblast differentiation by regulating Smad1/5/9, a member of the receptor‐regulated Smad (R‐Smad) family. In addition, osteoblast differentiation induced by Smad1/5/9 mediated increases in the expression of heme oxygenase 1 (HO‐1) has not been reported. This study investigated the effects of zingerone on osteoblast differentiation and confirmed the relationship between Smad1/5/9 and HO‐1. Zingerone increased the expression of osteogenic genes including runt‐related transcription factor 2 (Runx2), distal‐less homeobox (Dlx5) and osteocalcin (OC) and also promoted Smad1/5/9 phosphorylation. Interestingly, HO‐1 expression was also elevated by zingerone, and an inhibitor of HO‐1 (Sn[IV] protoporphyrin IX dichloride [SnPP]) suppressed the zingerone‐induced increase in HO‐1 expression and expression of osteogenic marker genes such as Dlx5, Runx2 and OC. Protein phosphatase 2A Cα (PP2A Cα, an inhibitor of Smad1/5/9) suppressed the zingerone‐induced increase in HO‐1 expression and expression of osteogenic marker genes. The zingerone‐induced increase in HO‐1 luciferase activity was suppressed by PP2A Cα. Taken together; our data demonstrate that zingerone promotes osteoblast differentiation by increasing Smad1/5/9 mediated HO‐1 expression.