Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2024; 15(4): 769-782
Published online Apr 15, 2024. doi: 10.4239/wjd.v15.i4.769
Icariin accelerates bone regeneration by inducing osteogenesis-angiogenesis coupling in rats with type 1 diabetes mellitus
Sheng Zheng, Guan-Yu Hu, Jun-Hua Li, Jia Zheng, Yi-Kai Li
Sheng Zheng, Guan-Yu Hu, Yi-Kai Li, Department of Traditional Chinese Orthopedics and Traumatology, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong Province, China
Jun-Hua Li, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Jia Zheng, Department of Endocrinology, Peking University First Hospital, Beijing 100034, China
Co-corresponding authors: Jia Zheng and Yi-Kai Li.
Author contributions: Zheng J and Li YK contributed equally to this work and are co-corresponding authors on this paper according to the critical roles they played throughout the research in experimental design, data analysis, and provision of intellectual ideas and methods; Zheng S, Zheng J, and Li YK designed the research study; Zheng S, Hu GY, and Li JH performed the research; Li JH and Zheng J contributed new reagents and analytic tools; Zheng S, Zheng J, and Li YK analyzed the data and wrote the manuscript; and all authors read and approved the final manuscript.
Supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation, No. GZC20231088; and President Foundation of The Third Affiliated Hospital of Southern Medical University, China, No. YP202210.
Institutional animal care and use committee statement: The study was reviewed and approved by the Animal Ethics Committee of Southern Medical University (Approval No. SMUL2022023).
Conflict-of-interest statement: The authors declare having no competing interests for this article.
Data sharing statement: Data will be made available upon reasonable request to the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yi-Kai Li, MD, PhD, Chief Physician, Full Professor, Professor, Research Scientist, Department of Traditional Chinese Orthopedics and Traumatology, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, No. 183 Zhongshan Avenue West, Tianhe District, Guangzhou 510630, Guangdong Province, China. ortho@smu.edu.cn
Received: December 31, 2023
Peer-review started: December 31, 2023
First decision: January 16, 2024
Revised: January 22, 2024
Accepted: March 5, 2024
Article in press: March 5, 2024
Published online: April 15, 2024
Processing time: 102 Days and 17.6 Hours
Abstract
BACKGROUND

Icariin (ICA), a natural flavonoid compound monomer, has multiple pharmacological activities. However, its effect on bone defect in the context of type 1 diabetes mellitus (T1DM) has not yet been examined.

AIM

To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.

METHODS

The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining, alizarin red S staining, quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis. A bone defect model was established in T1DM rats. The model rats were then treated with ICA or placebo and micron-scale computed tomography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.

RESULTS

ICA promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation. The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers (alkaline phosphatase and osteocalcin) and angiogenesis-related markers (vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1) compared to the untreated group. ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs. In the bone defect model T1DM rats, ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation. Lastly, ICA effectively accelerated the rate of bone formation in the defect area.

CONCLUSION

ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Keywords: Icariin; Osteogenesis-angiogenesis coupling; Type 1 diabetes mellitus; Bone defect; Bone regeneration

Core Tip: Type 1 diabetes mellitus (T1DM) leads to a decrease in bone formation in a bone defect area. We demonstrated that icariin, a natural flavonoid compound monomer, accelerated bone regeneration by inducing osteogenesis-angiogenesis coupling of bone marrow mesenchymal stem cells in a T1DM rat model. This finding indicates that further investigations into the effective coupling of osteogenesis and angiogenesis should be undertaken in the field of bone regeneration in T1DM patients.