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World J Stem Cells. May 26, 2026; 18(5): 117045
Published online May 26, 2026. doi: 10.4252/wjsc.v18.i5.117045
Published online May 26, 2026. doi: 10.4252/wjsc.v18.i5.117045
Hypoxia-preconditioned adipose-derived stem cell exosomes promote osteogenic differentiation and bone formation in bone marrow mesenchymal stem cells through the Piezo1/Ca2+ signaling axis
Wumiti Taxi, Jie Sun, Yi-Hua Zhu, Tian-Chi Zhang, Yang Guo, Ya-Lan Pan, Meng-Min Liu, Xi Chen, Li-Ning Wang, Yong Ma, Laboratory of New Techniques of Restoration & Reconstruction of Orthopedics and Traumatology, Nanjing University of Chinese Medicine, Nanjing 210046, Jiangsu Province, China
Yang Guo, Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Nanjing University of Chinese Medicine, Wuxi 210022, Jiangsu Province, China
Chun-Lei Zhang, Kai Tong, Department of Orthopedic ang Traumatology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210046, Jiangsu Province, China
Tao Jiang, Department of Orthopedic ang Traumatology, Changzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou 213300, Jiangsu Province, China
Co-first authors: Wumiti Taxi and Jie Sun.
Co-corresponding authors: Tao Jiang and Yong Ma.
Author contributions: Taxi W and Sun J contributed to the writing - original draft, they contributed equally to this manuscript and are co-first authors; Zhu YH, Zhang TC, and Chen X contributed to data curation and formal analysis; Guo Y, Pan YL, and Liu MM contributed to data curation; Zhang CL, Tong K, and Jiang T contributed to writing - review and editing; Guo Y, Pan YL, Liu MM, Zhang CL, Tong K, and Jiang T contributed to methodology; Taxi W, Sun J, and Wang LN contributed to the conceptualization; Ma Y and Jiang T contributed to acquisition and funding, they contributed equally to this manuscript and are co-corresponding authors.
AI contribution statement: We used the “Home for research AI Intelligent Polishing tool 2.0” for language polishing of the manuscript. We confirm that the” Home for research AI Intelligent Polishing 2.0 tool” was only used for language polishing and did not influence the scientific content, interpretation, or conclusions of the manuscript.
Supported by National Natural Science Foundation of China, No. 82474549, No. 82074458, No. 82174411, and No. 82505718; the Natural Science Foundation of Jiangsu Province, No. BK20221351, No. BK20220470, and No. BK20240745; the Jiangsu CM Clinical Innovation Center of Degenerative Bone and Joint Disease (Jiangsu Science and Education of Traditional Chinese Medicine)[2021], No. 4; the Natural Science Foundation of Jiangsu Higher Education Institutions, No. 22KJB360012; and Yancheng Basic Research Program General Project, No. YCBK2024087.
Institutional animal care and use committee statement: All experimental procedures were strictly performed in accordance with animal ethical welfare guidelines and were approved by the Experimental Animal Ethics Committee of Nanjing University of Chinese Medicine (Approval No. 202312A044).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets and Supplementary materials from this study are accessible upon reasonable request from the corresponding author.
Corresponding author: Yong Ma, Laboratory of New Techniques of Restoration & Recon
Received: November 28, 2025
Revised: December 26, 2025
Accepted: March 2, 2026
Published online: May 26, 2026
Processing time: 179 Days and 4.7 Hours
Revised: December 26, 2025
Accepted: March 2, 2026
Published online: May 26, 2026
Processing time: 179 Days and 4.7 Hours
Core Tip
Core Tip: This study reveals that exosomes derived from hypoxia-preconditioned adipose-derived stem cells significantly enhance osteogenic differentiation and bone formation through the Piezo1/calcium signaling axis. Hypoxia-preconditioned adipose-derived stem cells promote bone marrow mesenchymal stem cell mineralization and improve bone microarchitecture in an ovariectomized rat model. These effects are abolished by the Piezo1 inhibitor GsMTx4, identifying Piezo1 as a novel mechanistic target. Our findings propose a promising exosome-based strategy for the treatment of osteoporosis.