LncRNA MALAT1 as a Competitive Endogenous RNA in Osteoarthritis: Mechanisms and Therapeutic Prospects

¹ Department of Orthopedics, The Second Affiliated Hospital of Hunan Normal University (921 Hospital of Joint Logistics Support Force People’s Liberation Army of China), No.1 Hongshan Bridge, Sifangping Road, Kaifu District, Changsha, Hunan 410003, China,

JCNR 2026 , 10(3), 401–409; https://doi.org/10.26689/jcnr.v10i3.14620

© 2026 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Osteoarthritis (OA) is a complex degenerative joint disease characterized by articular cartilage degeneration, synovial inflammation, and osteophyte formation, with its exact pathogenesis not yet fully elucidated. In recent years, competing endogenous RNA (ceRNA) regulatory networks, particularly the role of long non-coding RNAs (LncRNAs) within them, have garnered increasing attention. This review focuses on LncRNA MALAT1, summarizing its ceRNA mechanism in the initiation and progression of OA. The article systematically elaborates on how MALAT1 acts as a molecular sponge to adsorb specific microRNAs (miRNAs), thereby relieving the inhibition of downstream target genes, and consequently regulating key pathological processes such as chondrocyte metabolism, extracellular matrix homeostasis, inflammatory response, and cell apoptosis. Furthermore, this review summarizes the potential value and latest research progress in targeting the MALAT1-ceRNA axis for early OA diagnosis, disease monitoring, and the development of novel therapeutic strategies, aiming to provide a new theoretical basis and perspective for the precise diagnosis and treatment of OA.

References

Sun K, Jing X, Guo J, et al., 2021, Mitophagy in Degenerative Joint Diseases. Autophagy, 17(9): 2082–2092.

Dilmaghnai N, Shoorei H, Sharifi G, et al., 2021, Non-Coding RNAs Modulate Function of Extracellular Matrix Proteins. Biomedicine & Pharmacotherapy, 136: 111240.

Hu K, Wen H, Song T, et al., 2024, Deciphering the Role of LncRNAs in Osteoarthritis: Inflammatory Pathways Unveiled. Journal of Inflammation Research, 17: 6563–6581.

Wang R, Shiu H, Lee W, 2022, Emerging Role of LncRNAs in Osteoarthritis: An Updated Review. Frontiers in Immunology, 13: 982773.

Alnajjar F, Sharma-Oates A, Wijesinghe S, et al., 2021, The Expression and Function of Metastases Associated Lung Adenocarcinoma Transcript-1 Long Non-Coding RNA in Subchondral Bone and Osteoblasts from Patients with Osteoarthritis. Cells, 10(4): 786.

Almeida R, Tuerlings M, Ramos Y, et al., 2023, Allelic Expression Imbalance in Articular Cartilage and Subchondral Bone Refined Genome-Wide Association Signals in Osteoarthritis. Rheumatology, 62(4): 1669–1676.

Song C, Wang Y, Pu J, et al., 2021, MALAT1 Alleviates Articular Chondrocyte Apoptosis and Matrix Degradation by Regulating miR-146a. Modern Immunology, 41(2): 111–117.

Gao Z, Guo C, Xiang S, et al., 2024, Suppression of MALAT1 Promotes Human Synovial Mesenchymal Stem Cells Enhance Chondrogenic Differentiation and Prevent Osteoarthritis of the Knee in a Rat Model via Regulating miR-212-5p/MyD88 Axis. Cell and Tissue Research, 395(3): 251–260.

Zhao Z, Liu M, Zha R, et al., 2025, Effect of LncRNA MALAT1/miR-15b-5p Regulating Wnt/β-Catenin Pathway on Lipopolysaccharide-Induced Chondrocyte Injury. Journal of Anhui Medical University, 60(7): 1231–1240.

Giordano R, Petersen K, Santoro M, et al., 2021, Circulating Long Non-Coding RNA Signature in Knee Osteoarthritis Patients with Postoperative Pain One-Year After Total Knee Replacement. Scandinavian Journal of Pain, 21(4): 823–830.

Pan C, Huang W, Chen Q, et al., 2021, LncRNA Malat-1 From MSCs-Derived Extracellular Vesicles Suppresses Inflammation and Cartilage Degradation in Osteoarthritis. Frontiers in Bioengineering and Biotechnology, 9: 772002.

Fu C, Lin Y, Lan S, et al., 2025, Mechanism of Tougu Xiaotong Capsules Regulating Malat1 and miR-16-5p ceRNA to Alleviate “Cholesterol-Iron” Metabolism Disorder in Osteoarthritis Chondrocytes. China Journal of Chinese Materia Medica, 50(15): 4363–4371.

Feng L, Yang Z, Li Y, et al., 2022, Malat1 Attenuated the Rescuing Effects of Docosahexaenoic Acid on Osteoarthritis Treatment via Repressing Its Chondroprotective and Chondrogenesis Activities. Biomedicine & Pharmacotherapy, 154: 113608.

Farzaneh M, Najafi S, Anbiyaee O, et al., 2023, LncRNA MALAT1-Related Signaling Pathways in Osteosarcoma. Clinical and Translational Oncology, 25(1): 21–32.

Zhao Y, Wang Z, Gao M, et al., 2021, LncRNA MALAT1 Regulated ATAD2 to Facilitate Retinoblastoma Progression via miR-655-3p. Open Medicine, 16(1): 931–943.

Li W, Huang Y, Wang H, et al., 2023, Mechanism of Quercetin Inhibiting Cartilage Injury and Chondrocyte Apoptosis in Knee Osteoarthritis Mice by Down-Regulating MALAT1. Chinese Journal of Osteoporosis and Bone Mineral Research, 16(1): 33–40.

Yuan Z, Huang Y, Sadikot R, 2023, Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 Promotes HIV-1 Replication through Modulating microRNAs in Macrophages. Journal of Virology, 97(6): e0005323.

Zhang G, Zhang H, You W, et al., 2020, Therapeutic Effect of Resveratrol in the Treatment of Osteoarthritis via the MALAT1/miR-9/NF-κB Signaling Pathway. Experimental and Therapeutic Medicine, 19(3): 2343–2352.

Wei L, Feng Z, Dou Q, et al., 2024, Metastasis-Associated Lung Adenocarcinoma Transcript 1 Overexpression in Testis Contributes to Idiopathic Non-Obstructive Azoospermia via Repressing ETS Variant Transcription Factor 5. Molecular Biomedicine, 5(1): 71.

Chen W, Wang F, Wang J, et al., 2022, The Molecular Mechanism of Long Non-Coding RNA MALAT1-Mediated Regulation of Chondrocyte Pyroptosis in Ankylosing Spondylitis. Molecules and Cells, 45(6): 365–375.

Lahimchi M, Mohammadnia-Afrouzi M, Baharlou R, et al., 2024, Decoding Inflammation: Glycoprotein A Repetition Predominant, microRNA-142-3-p, and Metastasis Associated Lung Adenocarcinoma Transcript 1 as Novel Inflammatory Biomarkers of Inflammatory Bowel Disease. Molecular Biology Reports, 51(1): 500.

Yang F, Shang W, Cai H, 2024, Correlation of lncRNA MALAT1 with Disease Activity and Inflammatory Factors in Patients with Rheumatoid Arthritis. Chinese Journal of Practical Diagnosis and Therapy, 38(9): 916–922.

Hong J, Ye F, Yu B, et al., 2020, Identification of the Specific microRNAs and Competitive Endogenous RNA Mechanisms in Osteoporosis. Journal of International Medical Research, 48(10): 300060520954722.

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