Asperosaponin VI promotes bone marrow stromal cell osteogenic differentiation through the PI3K/AKT signaling pathway in an osteoporosis model.

Ke Ke,Jue Shi,Xiaofeng Yang,Linfeng Chi,Zhijian Xie,Huali Shi,Lingling Hu,Yu Wang,Weijian Xu,Qi Li

doi:10.1038/srep35233

Abstract

Asperosaponin VI (ASA VI), a natural compound isolated from the well-known traditional Chinese herb Radix Dipsaci, has an important role in promoting osteoblast formation. However, its effects on osteoblasts in the context of osteoporosis is unknown. This study aimed to investigate the effects and mechanism of ASA VI action on the proliferation and osteogenic differentiation of bone marrow stromal cells isolated from the ovariectomized rats (OVX rBMSCs). The toxicity of ASA VI and its effects on the proliferation of OVX rBMSCs were measured using a CCK-8 assay. Various osteogenic differentiation markers were also analyzed, such as ALP activity, calcified nodule formation, and the expression of osteogenic genes, i.e., ALP, OCN, COL 1 and RUNX2. The results indicated that ASA VI promoted the proliferation of OVX rBMSCs and enhanced ALP activity and calcified nodule formation. In addition, while ASA VI enhanced the expression of ALP, OCN, Col 1 and RUNX2, treatment with LY294002 reduced all of these osteogenic effects and reduced the p-AKT levels induced by ASA VI. These results suggest that ASA VI promotes the osteogenic differentiation of OVX rBMSCs by acting on the phosphatidylinositol—3 kinase/AKT signaling pathway.

Highlights

Osteoporosis (OP), characterized by low bone mass and compromised bone strength, is a skeletal disease that commonly affects older, postmenopausal or estrogen-deficient women
Figure 1. 3D reconstructions of femoral metaphyseal trabecular structure were observed by micro-CT. (A) Bone mineral density (BMD) of SHAM group and OVX group was determined by micro-CT. (B) Bone volume/Total volume (BV/TV) (Percent bone volume) of SHAM group and OVX group was determined by micro-CT. (C)Trabecular Sepa ration/Spacing of SHAM group and OVX group was determined by micro-CT. (D) The alkaline phosphatase (ALP) expression of the two groups of Bone marrow stromal cells (BMSCs) were observed on 7d and 14d
We found that ASA VI played a role in the osteogenesis of BMSCs obtained from ovariectomized rats (OVX rBMSCs) and that this effect was dependent on the phosphatidylinositol—3 kinase (PI3K)/ AKT signaling pathway

Summary

Introduction

Osteoporosis (OP), characterized by low bone mass and compromised bone strength, is a skeletal disease that commonly affects older, postmenopausal or estrogen-deficient women. Radix Dipsaci total saponins induced osteoblastic differentiation through a bone morphogenic protein (BMP)-2/mitogen-activated protein kinase (MAPK)/ SMAD1/5/8-dependent runt-related transcription factor 2 (RUNX2) signaling pathway[18]. There are only a few reports on the osteogenic effects of ASA VI and only one report of it enhancing the proliferation and differentiation of MC3T3-E1 cells and primary rat osteoblasts[20]. We found that ASA VI played a role in the osteogenesis of BMSCs obtained from ovariectomized rats (OVX rBMSCs) and that this effect was dependent on the PI3K/ AKT signaling pathway

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