{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:48:58Z","timestamp":1780606138954,"version":"3.54.1"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:00:00Z","timestamp":1641340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is still controversial. One possible mechanism points to the homeostatic status of extracellular matrix (ECM) anabolism, and catabolism in the disc may play a vital role in the disease\u2019s progression. If the damaged disc receives an abundant amount of cartilage, anabolic factors may stimulate the residual cells in the damaged disc to secrete the ECM and mitigate the degeneration process. To examine this hypothesis, a cartilage anabolic factor, Runx1, was expressed by mRNA through a sophisticated polyamine-based PEG-polyplex nanomicelle delivery system in the damaged disc in a rat model. The mRNA medicine and polyamine carrier have favorable safety characteristics and biocompatibility for regenerative medicine. The endocytosis of mRNA-loaded polyplex nanomicelles in vitro, mRNA delivery efficacy, hydration content, disc shrinkage, and ECM in the disc in vivo were also examined. The data revealed that the mRNA-loaded polyplex nanomicelle was promptly engulfed by cellular late endosome, then spread into the cytosol homogeneously at a rate of less than 20 min post-administration of the mRNA medicine. The mRNA expression persisted for at least 6-days post-injection in vivo. Furthermore, the Runx1 mRNA delivered by polyplex nanomicelles increased hydration content by \u224843% in the punctured disc at 4-weeks post-injection (wpi) compared with naked Runx1 mRNA administration. Meanwhile, the disc space and ECM production were also significantly ameliorated in the polyplex nanomicelle group. This study demonstrated that anabolic factor administration by polyplex nanomicelle-protected mRNA medicine, such as Runx1, plays a key role in alleviating the progress of DDD, which is an imbalance scenario of disc metabolism. This platform could be further developed as a promising strategy applied to regenerative medicine.<\/jats:p>","DOI":"10.3390\/ijms23010565","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Runx1 Messenger RNA Delivered by Polyplex Nanomicelles Alleviate Spinal Disc Hydration Loss in a Rat Disc Degeneration Model"],"prefix":"10.3390","volume":"23","author":[{"given":"Cheng-Chung","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsi-Kai","family":"Tsou","sequence":"additional","affiliation":[{"name":"Functional Neurosurgery Division, Neurological Institute, Taichung Veterans General Hospital, Taichung 40705, Taiwan"},{"name":"Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli County 35664, Taiwan"},{"name":"College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan"},{"name":"College of Health, National Taichung University of Science and Technology, Taichung 40401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsu-Hsin","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long Yi","family":"Chan","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9813-2989","authenticated-orcid":false,"given":"Guan-Yu","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, College of Medicine, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoji","family":"Maeda","sequence":"additional","affiliation":[{"name":"Tsuzuki Institute for Traditional Medicine, College of Pharmacy, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, Kitaadachi-gun, Saitama 362-0806, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-7381","authenticated-orcid":false,"given":"Chin-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development, College of Medicine, China Medical 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