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Tendinopathy involves the inflammation and degeneration of the tendon due to repetitive strain injury. Current treatments primarily target inflammation resolution, yet they do not aim at tissue regeneration. In this study, a microfluidics approach is harnessed to develop a platform of lipid nanoparticles (LNPs) loaded simultaneously with SMAD3 siRNA and collagen I mRNA, aiming to explore its potential dual antifibrotic and regenerative effects in human tenocytes. The developed LNPs displayed size homogeneity and colloidal stability and exhibited high cytocompatibility in human tenocytes. Moreover, LNPs allowed for efficient uptake and transfection efficiency of the RNAs. In the efficacy studies, the gene expression and production of SMAD3 and collagen I were tested by real-time quantitative chain polymerase reaction and immuno- and intracellular staining, revealing collagen I production enhancement, SMAD3 inhibition, and modulation of other tendon repair factors by the LNPs. Overall, the potential of this platform of RNA-loaded LNPs to be used as a dual therapeutic approach to prevent fibrosis and promote tissue remodeling in late stages of tendon diseases was confirmed.
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http://dx.doi.org/10.1021/acsanm.4c02996 | DOI Listing |
J Orthop Sports Med
July 2025
Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, California, 91766, USA.
Diabetes mellitus is known to impair tendon structure and function, yet the molecular mechanisms linking hyperglycemia to tendon degeneration remain poorly understood. This study investigated the expression of early growth response-1 (EGR1) and its association with toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) signaling pathways in the rotator cuff tendons of hyperglycemic swine, a model chosen for its anatomical similarity to humans. Rotator cuff tendon tissues were collected from normal and hyperglycemic swine and analyzed using histology, qRT-PCR, Western blotting, and immunohistochemistry.
View Article and Find Full Text PDFInt J Mol Sci
July 2025
Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, Italy.
Tendinopathies are a significant challenge in musculoskeletal medicine, with current treatments showing variable efficacy. Electromagnetic transduction therapy (EMTT) has emerged as a promising therapeutic approach, but its biological effects on tendon cells remain largely unexplored. Here, we investigated the effects of EMTT on primary cultured human tenocytes' behavior and functions in vitro, focusing on cellular responses, senescence-related pathways, and molecular mechanisms.
View Article and Find Full Text PDFCurr Issues Mol Biol
July 2025
Department of Orthopaedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku, Kitasato, Sagamihara 252-0374, Kanagawa, Japan.
Rotator cuff tears are a leading cause of shoulder pain and dysfunction, yet the molecular mechanisms that link tendon injury to inflammation and nociceptive signaling remain poorly understood. Netrin-1, a classical axon guidance cue signaling through dependence receptors UNC5B and Neogenin-1, has been implicated in both neuronal plasticity and inflammatory processes, but its role in tendon pathology has not been explored. A rat supraspinatus tear model was employed to assess, in vivo, the expression of genes encoding netrin-1 () and its receptors ( and ) at 0, 7, 14, 28, and 56 days post-injury (n = 10 per time point).
View Article and Find Full Text PDFCureus
June 2025
Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, JPN.
Introduction: Rotator cuff tears are a major cause of shoulder dysfunction and pain, particularly in older adults, with re-tear rates remaining high despite surgical advances. Persistent inflammation and dysregulated extracellular matrix (ECM) remodeling contribute to impaired healing. Tumor necrosis factor-α (TNF-α) is known to drive tendon inflammation, but the downstream mediators linking TNF-α signaling to matrix degradation remain incompletely understood.
View Article and Find Full Text PDFCells
June 2025
Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Mangiagalli 31, 20133 Milan, Italy.
Local anesthetics (LAs) are frequently administered via peritendinous ultrasound-guided injections for diagnostic and therapeutic purposes. Since in vitro studies have demonstrated LAs' tenotoxic effects, raising concerns about their safety in infiltrative treatments, and since lidocaine (LD) emerged as one of the most cytotoxic LAs, we analyzed apoptosis, oxidative stress, and collagen turnover pathways in human tenocytes treated with LD, as well as the possible protection from LD-induced injury elicited by antioxidant ascorbic acid (AA). Tenocytes from gluteal tendons were treated with 0.
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