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World J Stem Cells. Jul 26, 2022; 14(7): 473-489
Published online Jul 26, 2022. doi: 10.4252/wjsc.v14.i7.473
Application of exosome-derived noncoding RNAs in bone regeneration: Opportunities and challenges
Yuan-Zhong Ren, Shan-Shan Ding, Ya-Ping Jiang, Hui Wen, Tao Li
Yuan-Zhong Ren, Hui Wen, Department of Emergency Trauma Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, Henan Province, China
Shan-Shan Ding, Department of Geriatrics, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, Henan Province, China
Ya-Ping Jiang, Department of Oral Implantology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Tao Li, Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
Author contributions: Ren YZ and Ding SS drafted and wrote the review; Wen H made critical revisions related to the necessary intellectual content of the manuscript; Jiang YP and Li T contributed study design and supervision; all authors read and approved the final version of the manuscript.
Supported by Qingdao Traditional Chinese Medicine Science and Technology Project, No. 2021-zyym28; and Science and technology Development Project of Shandong Geriatric Society, No. LKJGG2021W082.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Tao Li, MD, Postdoc, Surgeon, Department of Joint Surgery, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao 266003, Shandong Province, China. qdult@qdu.edu.cn
Received: March 19, 2022
Peer-review started: March 19, 2022
First decision: April 18, 2022
Revised: May 15, 2022
Accepted: July 8, 2022
Article in press: July 8, 2022
Published online: July 26, 2022
Processing time: 128 Days and 20.4 Hours
Abstract

With advances in the fields of regenerative medicine, cell-free therapy has received increased attention. Exosomes have a variety of endogenous properties that provide stability for molecular transport across biological barriers to cells, as a form of cell-to-cell communication that regulates function and phenotype. In addition, exosomes are an important component of paracrine signaling in stem-cell-based therapy and can be used as a stand-alone therapy or as a drug delivery system. The remarkable potential of exosomes has paved the pathway for cell-free treatment in bone regeneration. Exosomes are enriched in distinct noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs and circular RNAs. Different ncRNAs have multiple functions. Altered expression of ncRNA in exosomes is associated with the regenerative potential and development of various diseases, such as femoral head osteonecrosis, myocardial infarction, and cancer. Although there is increasing evidence that exosome-derived ncRNAs (exo-ncRNAs) have the potential for bone regeneration, the detailed mechanisms are not fully understood. Here, we review the biogenesis of exo-ncRNA and the effects of ncRNAs on angiogenesis and osteoblast- and osteoclast-related pathways in different diseases. However, there are still many unsolved problems and challenges in the clinical application of ncRNA; for instance, production, storage, targeted delivery and therapeutic potency assessment. Advancements in exo-ncRNA methods and design will promote the development of therapeutics, revolutionizing the present landscape.

Keywords: Exosomes; Non-coding RNA; Bone; Osteogenesis; Angiogenesis; Osteoclasts

Core Tip: The key to bone regeneration is the mutual balance between osteoblasts, osteoclasts and angiogenesis. As a critical factor in bone regeneration, exosome-derived noncoding RNA (exo-ncRNA) has been extensively studied. However, the detailed mechanism of exo-ncRNA in bone regeneration is still unclear, and further research is necessary. This article summarizes the research on exo-ncRNA in bone regeneration.