Icariin and Icariside II Reciprocally Stimulate Osteogenesis and Inhibit Adipogenesis of Multipotential Stromal Cells through ERK Signaling

Dawei Zhang,Jiantao Lin,Chao Wan,Ning Zhao,Jikun Du,Hongbo Wang,Hamid Tebyanian

doi:10.1155/2021/8069930

Abstract

Herba Epimedii is a famous Chinese herbal medicine for treating bone diseases. Icariin and icariside II, the main chemical constituents, have attracted great attention from scientists for their potential as antiosteoporosis agents. Our study aimed to evaluate their effects on the lineage commitment of multipotential stromal cells (MSCs). The osteogenesis and adipogenesis of MSCs were assessed by ALP activity, calcium deposition, and adipocyte formation. The expression profiles and levels of osteogenic and adipogenic specific genes were evaluated by cDNA microarray and quantitative real-time PCR. The involvement of extracellular signal-regulated kinase (ERK) signaling was studied by enzyme-linked immunosorbent assay. Icariin and icariside II significantly increased ALP activity and mineralization during osteogenic differentiation of MSCs. Runx2, Col1, and Bmp2 were upregulated in the presence of icariin and icariside II. Meanwhile, they downregulated Pparg, Adipsin, and Cebpb expression during adipogenic differentiation. cDNA microarray revealed 57 differentially expressed genes during lineage commitment of MSCs. In addition, icariin and icariside II enhanced the phosphorylation of ERK, and the above biological effects were blocked by ERK inhibitor U0126. Icariin and icariside II may drive the final lineage commitment of MSCs towards osteogenesis and inhibit adipogenesis through the ERK signaling pathway. Both of them exert multiple osteoprotective effects and deserve more attention for their medicinal and healthcare prospects.

Highlights

Herba Epimedii is a famous Chinese herbal medicine for treating bone diseases
Our study aimed to evaluate their effects on the lineage commitment of multipotential stromal cells (MSCs). e osteogenesis and adipogenesis of MSCs were assessed by ALP activity, calcium deposition, and adipocyte formation. e expression profiles and levels of osteogenic and adipogenic specific genes were evaluated by cDNA microarray and quantitative real-time PCR. e involvement of extracellular signal-regulated kinase (ERK) signaling was studied by enzyme-linked immunosorbent assay
0.01–10 μM icariin and icariside II more potently stimulated the proliferation of MSCs up to 30% (p < 0.05), respectively. e maximum effect was obtained at 0.1 μM for both icariin and icariside II, showing a tendency to decrease with increasing concentrations

Summary

Introduction

Herba Epimedii is a famous Chinese herbal medicine for treating bone diseases. Icariin and icariside II, the main chemical constituents, have attracted great attention from scientists for their potential as antiosteoporosis agents. Icariin and icariside II may drive the final lineage commitment of MSCs towards osteogenesis and inhibit adipogenesis through the ERK signaling pathway Both of them exert multiple osteoprotective effects and deserve more attention for their medicinal and healthcare prospects. Total flavonoids of Herba Epimedii (50 or 100 μg/g) were able to suppress urinary calcium excretion as well as loss of bone mass and strength at the distal femur and improve trabecular bone microarchitecture in OVX mice [6]. Icariin (10 μM) may recover the decreased osteogenic differentiation and bone formation function of MSCs from OVX rats [15] These studies were focused on the protective and osteogenic effects of icariin in MSCs. e reciprocal regulation potential of icariin and its metabolites during osteogenesis and adipogenesis of MSCs remains unclear. We aimed to investigate how icariin and its main metabolite (icariside II) modulate the lineage commitment of MSCs

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