Background: Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability.
Purpose: The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes.
Methods: LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog () has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA).
Results: In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism.
Conclusion: This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes.
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http://dx.doi.org/10.2147/IJN.S142797 | DOI Listing |
Pharmaceutics
December 2024
Laboratorio RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano, 1/10, 40136 Bologna, Italy.
The treatment of articular cartilage damage has always represented a problem of considerable practical interest for orthopedics. Over the years, many surgical techniques have been proposed to induce the growth of repairing tissue and limit degeneration. In 1994, the turning point occurred: implanted autologous cells paved the way for a new treatment option based more on regeneration than repair.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.
Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of cartilage and the subsequent inflammation of joint tissues, leading to pain and reduced mobility. Despite advancements in symptomatic treatments, disease-modifying therapies for OA remain limited. This narrative review examines the dual role of autophagy in OA, emphasizing its protective functions during the early stages and its potential to contribute to cartilage degeneration in later stages.
View Article and Find Full Text PDFJ Clin Med
December 2024
Department of Anatomy, Division of Basic Medicine, Tokai University School of Medicine, Isehara 259-1193, Kanagawa, Japan.
Osteoarthritis is caused by damage to the articular cartilage due to bone-on-bone collisions and friction. The length, width, and thickness of the ligaments are expected to change in order to regulate excessive bone-to-bone movement. We aimed to clarify the relationship between ligament morphology and joint surface degeneration in the ankle joints using macroscopic observations and measurements.
View Article and Find Full Text PDFJ Clin Med
December 2024
Department of Orthopedics and Traumatology, Paracelsus Medical University, Breslauer Strasse 201, 90471 Nuremberg, Germany.
Osteoarthritis (OA) of the knee is the most common joint disease, characterized by the degeneration of joint cartilage. Intra-articular hyaluronic acid (IAHA) injections are a well-established non-surgical treatment. This retrospective study analyzed knee OA patients receiving IAHA combined with niacinamide injections, assessing pain reduction in relation to patient data, the number of injections, and radiological findings.
View Article and Find Full Text PDFCells
December 2024
Department of Surgery, Divisions of Orthopaedic and Neurosurgery, University of Toronto, 661 University Ave., Suite 13-1387, Toronto, ON M5G 0B7, Canada.
Pain and disability secondary to degenerative disc disease continue to burden the healthcare system, creating an urgent need for effective, disease-modifying therapies. Contemporary research has identified potential therapies that include protein-, cellular- and/or matrix-related approaches; however, none have yet achieved a meaningful clinical impact. The tissue-specific realities of the intervertebral disc create considerable therapeutic challenges due to the disc's location, compartmentalization, hypovascularization and delicate physiological environment.
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