Matn3, also known as matrilin-3, is a member of the extracellular matrix (ECM) protein family. It plays essential roles in maintaining the integrity of the extracellular matrix, and is associated with pathways such as ECM-receptor interaction [5]. Matrilin-3 is of great biological importance in processes related to joint health and potentially in cancer development [1,2,3,5,6,7,9]. Genetic models, especially KO/CKO mouse models, can be valuable in further elucidating its functions.

In knee osteoarthritis, both SMSC-Exo (synovial mesenchymal stem cell-derived exosomes) and overexpression of Matn3 alleviated cartilage destruction and suppressed ECM degradation. SMSC-Exo achieved chondroprotective effects through delivering Matn3/IL-17A, and Matn3 could suppress the activation of PI3K/AKT/mTOR signaling through IL-17A [1]. In gastric cancer, Matn3 promotes cell proliferation, migration, and invasion. Knockdown of Matn3 inhibits these malignant behaviors and induces apoptosis. High Matn3 expression is related to poor prognosis in gastric cancer patients [2,3,5,6,7]. In intervertebral disc degeneration, reduced Matn3 can be considered a characteristic. Exosomal Matn3 of urine-derived stem cells ameliorates intervertebral disc degeneration by promoting nucleus pulposus cell (NPC) proliferation and ECM synthesis via activating TGF-β [4]. Also, a MATN3 gene polymorphism (SNP6 rs8176070) is associated with osteoarthritis in the Chinese Han population [8].

In conclusion, Matn3 is crucial for maintaining the extracellular matrix in joints and has significant impacts on osteoarthritis and cancer. Mouse models and other functional studies have revealed its role in cartilage protection in osteoarthritis, and its oncogenic role in gastric cancer. Understanding Matn3 functions through these research models provides valuable insights into the mechanisms of these diseases, potentially leading to new therapeutic strategies.

References:

1. Long, Long, Zou, Guoyou, Cheng, Yi, Wu, Hao, Shen, Yixin. 2023. MATN3 delivered by exosome from synovial mesenchymal stem cells relieves knee osteoarthritis: Evidence from in vitro and in vivo studies. In Journal of orthopaedic translation, 41, 20-32. doi:10.1016/j.jot.2023.06.003. https://pubmed.ncbi.nlm.nih.gov/37635810/

2. Li, Jing, Xie, Bo, Wang, Hu, Wang, QingKang, Wu, YongYou. . Investigating MATN3 and ASPN as novel drivers of gastric cancer progression via EMT pathways. In Human molecular genetics, 33, 2035-2050. doi:10.1093/hmg/ddae129. https://pubmed.ncbi.nlm.nih.gov/39301785/

3. Wang, Pan, Xiao, Wei-Sheng, Li, Yue-Hua, Zhu, Hong-Bo, Tan, Ye-Ru. 2021. Identification of MATN3 as a Novel Prognostic Biomarker for Gastric Cancer through Comprehensive TCGA and GEO Data Mining. In Disease markers, 2021, 1769635. doi:10.1155/2021/1769635. https://pubmed.ncbi.nlm.nih.gov/34900024/

4. Guo, Zhu, Su, WeiLiang, Zhou, RongYao, Chen, BoHua, Xiang, HongFei. 2021. Exosomal MATN3 of Urine-Derived Stem Cells Ameliorates Intervertebral Disc Degeneration by Antisenescence Effects and Promotes NPC Proliferation and ECM Synthesis by Activating TGF-β. In Oxidative medicine and cellular longevity, 2021, 5542241. doi:10.1155/2021/5542241. https://pubmed.ncbi.nlm.nih.gov/34136064/

5. Li, Ding, Xu, Jianqiu, Dong, Xiaochen, Pan, Jingye, Huang, Yueyue. . Diagnostic and prognostic value of MATN3 expression in gastric carcinoma: TCGA database mining. In Journal of gastrointestinal oncology, 12, 1374-1383. doi:10.21037/jgo-21-267. https://pubmed.ncbi.nlm.nih.gov/34532095/

6. Zhu, Wenjun, Fu, Min, Li, Qianxia, Peng, Xiaohong, Hu, Guangyuan. 2024. Amino acid metabolism-related genes as potential biomarkers and the role of MATN3 in stomach adenocarcinoma: A bioinformatics, mendelian randomization and experimental validation study. In International immunopharmacology, 143, 113253. doi:10.1016/j.intimp.2024.113253. https://pubmed.ncbi.nlm.nih.gov/39353384/

7. Wu, Ping-Li, He, Yi-Fu, Yao, Han-Hui, Hu, Bing. 2018. Martrilin-3 (MATN3) Overexpression in Gastric Adenocarcinoma and its Prognostic Significance. In Medical science monitor : international medical journal of experimental and clinical research, 24, 348-355. doi:. https://pubmed.ncbi.nlm.nih.gov/29343680/

8. Gu, Jiaao, Rong, Jiesheng, Guan, Fulin, Guan, Guofa, Tao, Tianzun. 2012. MATN3 gene polymorphism is associated with osteoarthritis in Chinese Han population: a community-based case-control study. In TheScientificWorldJournal, 2012, 656084. doi:10.1100/2012/656084. https://pubmed.ncbi.nlm.nih.gov/22973175/

9. Qin, Chongjiu, Qin, Haifei, Xie, Haixiang, Peng, Tao, Zhu, Guangzhi. 2025. The Role of MATN3 in Cancer Prognosis and Immune Infiltration Across Multiple Tumor Types. In Journal of Cancer, 16, 1519-1537. doi:10.7150/jca.103523. https://pubmed.ncbi.nlm.nih.gov/39991588/