Polydatin Ameliorates Osteoporosis via Suppression of the Mitogen-Activated Protein Kinase Signaling Pathway.

Ze Lin,Guohui Liu,Chenchen Yan,Xudong Xie,Hang Xue,Wu Zhou,Yun Sun,Adriana C Panayi,Yiqiang Hu,Liangcong Hu,Lang Chen,Yuan Xiong,Bobin Mi

doi:10.3389/fcell.2021.730362

Abstract

Purpose: Polydatin (POL) is a natural active compound found in Polygonum multiflorum with reported anti-oxidant and antiviral effects. With the aging population there has been a stark increase in the prevalence of osteoporosis (OP), rendering it an imposing public health issue. The potential effect of POL as a therapy for OP remains unclear. Therefore, we sought to investigate the therapeutic effect of POL in OP and to elucidate the underlying signaling mechanisms in its regulatory process.Methods: The POL-targeted genes interaction network was constructed using the Search Tool for Interacting Chemicals (STITCH) database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG). Pathways involved in OP and POL-targeted genes were identified. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the osteogenic genes and the phosphorylation level in pre-osteoblastic cells. In addition, ALP and alizarin red staining was used to test the effect of POL on extracellular matrix mineralization.Results: Twenty-seven KEGG pathways shared between POL-related genes and OP were identified. MAPK signaling was identified as a potential key mechanism. In vitro results highlighted a definitive anti-OP effect of POL. The phosphorylation levels of MAPK signaling, including p38α, ERK1/2, and JNK, were significantly decreased in this regulatory process.Conclusion: Our results suggest that POL has a promising therapeutic effect in OP. MAPK signaling may be the underlying mechanism in this effect, providing a novel sight in discovering new drugs for OP.

Highlights

Osteoporosis (OP), a condition characterized by thin and brittle bones, compromises bone strength and predisposes bones to fractures, especially the bones in the hip, spine, and wrist (Cummings and Melton, 2002; Compston et al, 2019)
Twenty-seven Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways shared between POL-related genes and OP were identified
mitogen-activated protein kinase (MAPK) signaling may be the underlying mechanism in this effect, providing a novel sight in discovering new drugs for OP

Summary

Introduction

Osteoporosis (OP), a condition characterized by thin and brittle bones, compromises bone strength and predisposes bones to fractures, especially the bones in the hip, spine, and wrist (Cummings and Melton, 2002; Compston et al, 2019). Studies have suggested that approximately one in two women and up to one in four men aged 50 and older will suffer a bone fracture due to OP (Sambrook and Cooper, 2006; Rachner et al, 2011; Compston et al, 2019). Design and development of effective drugs that can delay the pathological progress of OP have the potential to revolutionize healthcare provision. Owing to their low toxicity, natural active compounds of a plant origin are attracting attention (Zhu et al, 2018; Suroowan and Mahomoodally, 2019). A recent study reported that POL has anti-OP activity in ovariectomized mice (Shen et al, 2020). To the best of our knowledge, the mechanism of POL’s anti-OP activity remains elusive and requires further investigation

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Discussion

Conclusion