Icariin promotes cell adhesion for osteogenesis in bone marrow stromal cells via binding to integrin α5β1

Christina Chui-Wa Poon; Chun Au-Yeung; Ka-Ying Wong; Zoe Chan; Li-Ping Zhou; Gang Li; Yan Wang; Yan Zhang; Man-Sau Wong

doi:10.1016/j.phymed.2024.155887

Icariin promotes cell adhesion for osteogenesis in bone marrow stromal cells via binding to integrin α5β1

Phytomedicine. 2024 Oct:133:155887. doi: 10.1016/j.phymed.2024.155887. Epub 2024 Jul 16.

Authors

Christina Chui-Wa Poon¹, Chun Au-Yeung², Ka-Ying Wong², Zoe Chan², Li-Ping Zhou³, Gang Li⁴, Yan Wang⁴, Yan Zhang⁵, Man-Sau Wong⁶

Affiliations

¹ Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, PR China.; Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, PR China.
² Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, PR China.
³ School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, PR China.
⁴ Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China.
⁵ Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
⁶ Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, PR China.; Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, PR China.; State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PR China.. Electronic address: man-sau.wong@polyu.edu.hk.

PMID: 39067311
DOI: 10.1016/j.phymed.2024.155887

Abstract

Background and purpose: Icariin, an 8-prenylated flavonoid glycoside, is an anabolic agent that could exert rapid estrogenic actions via ligand-independent activation of estrogen receptor alpha (ERα) in osteoblastic cells to promote osteogenesis. However, relatively little is known about its direct cellular target, its protective effects, and cell adhesion activities in bone marrow stromal cells (BMSCs) against microgravity. In the present study, the effects of icariin on osteogenesis and cell adhesion under microgravity were examined with the involvement of integrin receptor α5β1, connexin 43, and CAMs.

Study design and methods: Icariin was orally administered to 6-month-old ovariectomized (OVX) Sprague-Dawley (SD) rats for 3 months through daily intake of phytoestrogen-free rodent diets containing icariin at 2 different dosages (50 and 500 ppm). BMSCs were harvested for experiments and RNA-sequencing analysis to examine the mechanism of action of icariin and its direct cellular target in stimulating osteogenesis.

Results: The results revealed that icariin induced the expression of cell adhesion molecules (CAMs) and protected against microgravity-induced disruption of actin cytoskeleton and the loss of osteogenic activities in BMSCs through the activation of connexin-43 (Cx43) and Ras homolog family member A (RhoA) and Rac family small GTPase 1 (Rac1)-mediated signaling pathways. Computerized molecular docking techniques and the competitive solid-phase binding ELISA assay confirmed that icariin could be a direct ligand of integrin alpha 5 beta 1 (α5β1), and it could also increase the protein expression of integrin α5β1 for mechanosensing.

Conclusion: Our findings suggest that icariin could directly activate cell adhesion signaling by binding to integrin α5β1, which opens up new avenues for the development of integrin α5β1 ligand as an agent to protect against unloading-induced bone loss.

Keywords: Bone marrow stromal cells; Cell adhesion; Icariin; Integrin; Microgravity.

MeSH terms

Animals
Cell Adhesion* / drug effects
Connexin 43* / metabolism
Female
Flavonoids* / pharmacology
Integrin alpha5beta1* / metabolism
Mesenchymal Stem Cells* / drug effects
Osteogenesis* / drug effects
Ovariectomy
Rats
Rats, Sprague-Dawley*

Substances

icariin
Flavonoids
Integrin alpha5beta1
Connexin 43
Gja1 protein, rat