2. Academic Validation
  3. Icariin regulates osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells in postmenopausal osteoporosis, potentially via the AMPK-mTOR-autophagy pathway

Icariin regulates osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells in postmenopausal osteoporosis, potentially via the AMPK-mTOR-autophagy pathway

  • Toxicol Appl Pharmacol. 2026 May:510:117761. doi: 10.1016/j.taap.2026.117761.
Yuqing Zeng 1,  Haitao Wang 2,  Jingtao Hu 3,  Weiwei Ruan 4,  Zhicheng Yao 5,  Binfeng Jiang 4,  Shu Deng 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, TongDe Hospital of Zhejiang Province, HangZhou 310012, ZheJiang, China; Zhejiang Institute of Traditional Chinese Medicine, HangZhou 310012, ZheJiang, China.
  • 2 Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University (College of Integrated Traditional Chinese and Western Medicine Clinical Medicine), Hangzhou, Zhejiang, China.
  • 3 Department of Orthopaedics, Hangzhou Hospital of Traditional Chinese Medicine, 453 Stadium Road, Hangzhou 310007, Zhejiang, China.
  • 4 Department of Orthopedics, TongDe Hospital of Zhejiang Province, HangZhou 310012, ZheJiang, China.
  • 5 The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.
  • 6 Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, ZheJiang, China. Electronic address: [email protected].
PMID: 41702462 DOI: 10.1016/j.taap.2026.117761
Abstract

Background: Postmenopausal osteoporosis (PMOP) is a bone disease resulting from estrogen deficiency. This investigation explores the impact of icariin (Ica) on PMOP.

Methods: Bilateral ovariectomy was performed to establish an ovariectomized (OVX) mouse model, followed by Ica administration. Bone parameters were measured using micro computed tomography. Fat content was evaluated using hematoxylin-eosin staining. Osteogenic/adipogenic differentiation of mouse bone marrow mesenchymal stem cells (BMSCs) was analyzed by Alkaline Phosphatase, Alizarin Red S, and Oil Red O staining. Reverse transcription-quantitative polymerase chain reaction measured bone and lipid marker gene expression. Transcriptome Sequencing and cell counting kit-8 were conducted, and the expression of AMPK-mTOR-autophagy pathway proteins and bone and lipid marker proteins was detected by immunohistochemistry and Western blot. Autophagy inhibitor 3-Methyladenine (3-MA) and AMPK Inhibitor dorsomorphin were employed to validate the role of Autophagy and AMPK in Ica treatment of PMOP.

Results: Ica treatment raised bone mass while reducing fat content in OVX mice in a dose-dependent manner. Ica promoted osteogenesis and inhibited adipogenesis in BMSCs from OVX mice. Transcriptome Sequencing showed that Autophagy and mTOR pathways were involved in PMOP. Ica reduced mTOR and p62 expression and increased LC3 expression in OVX mice and their BMSCs, and 3-MA reversed this phenomenon. The AMPK pathway was downregulated in OVX mice and their BMSCs, but was activated following Ica treatment. The application of dorsomorphin altered the expression of AMPK-mTOR-autophagy pathway in Ica-treated BMSCs.

Conclusion: Ica alleviates PMOP by regulating osteogenic/adipogenic differentiation of BMSCs, which may involve the AMPK-mTOR-autophagy pathway.

Keywords

AMPK; Autophagy; Icariin; Osteogenic/adipogenic differentiation; Postmenopausal osteoporosis.

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