Skip to main content

ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1510561
This article is part of the Research Topic Herbal Medicines and Their Metabolites as Therapeutic Agents in Osteolytic Disease Management View all 4 articles

Icariin Modulates Osteogenic and Adipogenic Differentiation in ADSCs via the Hippo-YAP/TAZ Pathway: A Novel Therapeutic Strategy for Osteoporosis

Provisionally accepted
Shaozi Lin Shaozi Lin 1Zuyu Meng Zuyu Meng 1*Mei Wang Mei Wang 1*Zixuan Ye Zixuan Ye 2Mengsha Long Mengsha Long 1*Yiyao Zhang Yiyao Zhang 1*Fang Liu Fang Liu 1*Hongling Chen Hongling Chen 1*Menghan Li Menghan Li 1*Jiajia Qin Jiajia Qin 1*Haiquan Liu Haiquan Liu 2*
  • 1 School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
  • 2 Huizhou Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China

The final, formatted version of the article will be published soon.

    Background: Adipose-derived stem cell (ADSC) transplantation presents a promising approach for osteoporosis (OP) treatment. However, the therapeutic efficacy of ADSCs is hindered by low post-transplantation survival rates and limited capacities for adhesion, migration, and differentiation. Icariin (ICA), the primary active compound of Epimedium, has been shown to promote cell proliferation and induce osteogenic differentiation; however, its specific effects on ADSC osteogenesis and the mechanisms by which ICA enhances osteoporosis treatment through cell transplantation remain inadequately understood. Purpose: This study investigates the effects of different concentrations of ICA on the osteogenic and adipogenic differentiation of rat ADSCs, aiming to elucidate the underlying mechanisms. ADSCs were isolated from female SPF-grade SD rats, with surface markers identified through flow cytometry. Osteogenic and adipogenic differentiation were assessed using Alizarin Red and Oil Red O staining, respectively. Third-generation ADSCs were divided into five groups: control, resveratrol (100 μmol/L), and four ICA treatment groups (1, 10, 50, and 100 μmol/L). Western blotting was performed to analyze the expression of factors associated with the Hippo-YAP/TAZ signaling pathway and the adipogenic marker PPARγ. Additionally, ADSCs were labeled with lentiviruses carrying enhanced green fluorescent protein (EGFP) and 5-bromo-2-deoxyuridine (BrdU) to assess their in vivo distribution, survival, proliferation, and differentiation of ADSCs post-ICA intervention. Results: In vitro, ICA significantly inhibited the Hippo pathway, reducing YAP and TAZ phosphorylation and enhancing their transcriptional activity, while simultaneously suppressing PPARγ. This promoted osteogenesis and inhibited adipogenesis in ADSCs. In vivo, ICA-treated ADSCs demonstrated effective distribution, survival, and osteogenic differentiation following subcutaneous injection into allogeneic rats. Conclusion: Our study demonstrates that ICA significantly enhances the osteogenic differentiation of ADSCs while inhibiting adipogenesis, providing novel insights and therapeutic strategies for osteoporosis and related conditions. Keywords: Icariin; Adipose-derived stem cells; Hippo-YAP/TAZ; Osteogenic; Adipogenesis

    Keywords: Icariin, adipose-derived stem cells, HIPPO-YAP/TAZ, Osteogenic, Adipogenesis

    Received: 13 Oct 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Lin, Meng, Wang, Ye, Long, Zhang, Liu, Chen, Li, Qin and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zuyu Meng, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
    Mei Wang, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
    Mengsha Long, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
    Yiyao Zhang, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
    Fang Liu, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
    Hongling Chen, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
    Menghan Li, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
    Jiajia Qin, School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong Province, China
    Haiquan Liu, Huizhou Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.