Delivery of FGF18 using mRNA-LNP protects the cartilage against degeneration via alleviating chondrocyte senescence

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 22, 2025

Osteoarthritis (OA) is a degenerative joint disease with an immense unmet medical need. FGF18 protein potential regenerative factor for cartilage repair. However, traditional delivery methods have limited efficacy due to the short lifetime and shallow infiltration. In this work, we discovered that lipid nanoparticle (LNP) can infiltrate deliver mRNA deeper in than proteins. After UTR optimization chemical modification, expression of last up 6 days cartilage. Furthermore, delivering activates FOXO3a-autophagy pathway, which protects against chondrocyte degeneration senescence. Local intra-articular injection mRNA-LNP significantly alleviates OA symptoms DMM senile models. Sustained accessibility FGF18-mRNA chondrocytes makes LNP-mRNA more effective recombinant protein. summary, study presents novel approach superior alone holds promise as new therapeutic strategy OA.

Language: Английский

Identification of WDR74 and TNFRSF12A as biomarkers for early osteoarthritis using machine learning and immunohistochemistry

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 28, 2025

Background Osteoarthritis (OA) is a chronic joint condition that causes pain, limited mobility, and reduced quality of life, posing threat to healthy aging. Early detection crucial for improving prognosis. Recent research has focused on the role ubiquitination-related genes (URGs) in early OA prediction. This study aims integrate URG expression data with machine learning (ML) identify biomarkers improve diagnosis prognosis stages OA. Methods single-cell RNA sequencing datasets were collected from GEO database. Single-cell analysis was performed investigate composition relationships chondrocytes The potential intercellular communication mechanisms explored using CellChat R package. URGs retrieved GeneCards, ubiquitination scores calculated AUCell Gene module based co-expression network conducted core genes. Additionally, ML construct diagnostic model. We employed XGBoost, gradient-boosting algorithm, model’s performance evaluated area under curve (AUC) receiver operating characteristic (ROC) curve. In addition, we relationship between immune processes. ChEA3 database utilized predict transcription factors regulated by select validated qRT-PCR immunohistochemistry (IHC). Results identified WDR74 TNFRSF12A as pivotal associated OA, exhibiting considerable differential expression. model constructed exhibited remarkable accuracy, values consistently exceeding 0.9. levels significantly higher IL-1β-induced group an vitro qPCR experiment. IHC validation human knee specimens confirmed upregulation tissues, corroborating their biomarkers. Conclusions principal highlighted attractiveness therapeutic targets. identification might facilitate intervention options, potentially modifying illness trajectory enhancing patient outcomes.

Language: Английский

Manganese Empowered Electronic Modulated Nanocatalysts Facilitate Bone Reconstruction via Osteoclastogenesis Inhibition and Osteogenesis Activation Bistimulatory Strategy

Composites Part B Engineering, Journal Year: 2025, Volume and Issue: unknown, P. 112364 - 112364

Published: March 1, 2025

Language: Английский