Hydroxysafflor yellow A promotes osteogenesis and bone development via epigenetically regulating β-catenin and prevents ovariectomy-induced bone loss.

Peng Wang,Min Wang,Meng Zhang,Weiping Lin,Haibin Wang,Chi Zhou,Lingli Ding,Ying Li,Liangliang Xu,Gang Li,Jinfang Zhang,Tingling Zhuo

doi:10.1016/j.biocel.2021.106033

Abstract

In clinical treatment, there is increasingly prevalent that traditional Chinese medicine treats common bone diseases including osteoporosis. Hydroxysafflor yellow A (HSYA), one of the essential compounds of Safflower, has been used as the therapy for thrombus, myocardial ischemia, and inflammation, but its effect on osteogenesis through epigenetic control and ovariectomy-induced bone loss in vivo has not been explored. Therefore, the study aimed to explore the function and mechanism of HSYA on bone formation and development. We found HSYA could enhance the cell viability and promote osteogenesis of hBMSCs in vitro. Mechanistically, HSYA could increase the expression of β-catenin leading to its accumulation in the nucleus and activation of downstream targets to promote osteogenesis. Besides, RNA-seq and quantitative RT-PCR and western blot showed KDM7A was significantly increased by HSYA. The occupancy of H3K27me2 on β-catenin promoter was significantly decreased by HSYA, which could be reversed by silencing endogenous KDM7A. More importantly, HSYA promoted bone development in chick embryos and prevented ovariectomy (OVX)-induced bone loss in SD rats. Taken together, our study has shown convincing evidence that HSYA could promote osteogenesis and bone development via epigenetically regulating β-catenin and prevent ovariectomy-induced bone loss.

Highlights

Bone is a complex tissue which protects our various soft tissues and maintains the mineral metabolism in the microenvironment [1]
We focused on the potential therapeutic effects of Hydroxysafflor yellow A (HSYA) on osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro and the chick embryo and ovariectomy (OVX)-induced osteoporosis rat model in vivo
HSYA had no effect on hBMSCs viability

Summary

Introduction

Bone is a complex tissue which protects our various soft tissues and maintains the mineral metabolism in the microenvironment [1]. The long bone development starts through Cartilaginous Internalized Bone when MSCs proliferate and densify into osteoblasts that secrete the osteoid and turn into bone cells [2]. MSCs are capable of self-replication and have multiple differentiation potential, including the osteoblast and the adipocyte. Osteogenesis and adipogenesis of MSCs are strictly regulated under various physiological signal transduction pathways to maintain dynamic balance. The ability to form adipocytes of MSCs will be inhibited when MSCs differentiate toward osteoblasts, and vice versa [3]. Excessive adipocytes have been proven to be the pathogenesis of several bone disorders, including osteoporosis [4], which may be related to bone loss

Objectives

Methods

Results

Discussion

Conclusion