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REVIEW
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Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications

Yuting Shen1,2# ,  Jiaying Xiong1,2# ,  Yuchen Zhang1,2# ,  Zhifei Gao1,2# ,  Changhai Ding3,4,5* ,  Yao Lu1,2,3,4*
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1 Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
2 The Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
3 Clinical Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
4 State Key Laboratory of Multi-organ Injury Prevention and Treatment, Southern Medical University, Guangzhou, Guangdong, China
5 Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
BMT, 00011 https://doi.org/10.12336/bmt.25.00011
Submitted: 16 March 2025 | Revised: 19 May 2025 | Accepted: 26 May 2025 | Published: 25 June 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Bone and joint diseases, including bone fractures, osteoarthritis, and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. Conservative therapy and surgical treatment do not always achieve satisfactory outcomes in orthopedics, especially for degenerative bone and joint diseases. Messenger RNA (mRNA) therapy refers to the production of functional proteins and peptides by introducing mRNA into the body. The success of mRNA vaccines during the COVID-19 pandemic highlights the unique advantages of mRNA therapy, including biocompatibility, avoidance of genomic integration, and flexible, sustained delivery. These features make mRNA therapy a versatile therapeutic modality for the treatment of orthopedic diseases. In this review, we first provide an overview of the latest advances in mRNA therapy. We introduce structural modifications of mRNA and advanced gene-editing technologies, including modifications to nucleosides, mRNA domains, and codon sequences. We then discuss the development of mRNA delivery systems, such as nanomaterials, biomimetic carriers, and hydrogels, which enhance mRNA stability, reduce immunogenicity, and improve targeted delivery. This review also explores the application of mRNA therapy in orthopedic diseases, with a particular focus on its utilization in treating bone tumors and degenerative disorders. Despite promising developments, several challenges remain, including optimizing delivery efficiency, prolonging protein expression, and addressing tissue-specific barriers. Accordingly, the current limitations and future directions of mRNA therapy in orthopedic applications are emphasized. In conclusion, mRNA therapy holds great promise and may open new avenues for the treatment of orthopedic diseases and related fields.

Keywords
Messenger RNA
Bone and joint diseases
mRNA modifications
Delivery system
mRNA therapy
Funding
This work was supported by the National Natural Science Foundation of China (Grant No. 82372374), the Guangdong Basic and Applied Basic Research Foundation (Grant No. 2024B1515020015), and the Science and Technology Program of Guangzhou (Grant No. 2024A04J4713).
Conflict of interest
The authors declare that they have no conflicts of interest.
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