IGF2 secreted from mesenchymal stem cells with high glutathione levels alleviates osteoarthritis via paracrine rejuvenation of senescent chondrocytes DOI Creative Commons
Gun Hee Cho, Hyun Cheol Bae, Yu Jeong Lee

et al.

Biomaterials Research, Journal Year: 2025, Volume and Issue: 29

Published: Jan. 1, 2025

Senescent chondrocytes, which are increased in osteoarthritic (OA) cartilage, promote cartilage defects and the senescent knee microenvironment by inducing senescence to surrounding normal chondrocytes secreting senescence-associated secretory proteins. Many studies have used mesenchymal stem cells (MSCs) treat OA, but MSC treatment remains challenging for clinical application owing quality control, engraftment, fibrocartilage regeneration. Here, rather than relying on direct regeneration of MSCs, we present a novel strategy suppress OA MSC-mediated chondrocyte targeting via paracrine activity thereby improving microenvironment. First, enable control umbilical cord priming MSCs supplementing human platelet lysate (hPL) greatly enhanced functions increasing cellular glutathione levels throughout serial passaging. Intra-articular injection primed successfully suppressed progression accumulation without Indirect coculture with using transwell ameliorated phenotypes suggesting rejuvenation. Based secretome analysis, identified insulin-like growth factor 2 (IGF2) as key component that induces rejuvenation MSCs. The effects IGF2 act through autophagy activation up-regulation autophagy-related gene expression autophagic flux. To cross-validate secreted vivo, knockdown substantially abolished its therapeutic efficacy rabbit model. Collectively, these findings demonstrate hPL supplementation enables levels. mechanism was IGF2, activating autophagy.

Language: Английский

Identification and Validation of Pivotal Genes in Osteoarthritis Combined with WGCNA Analysis DOI Creative Commons
Chun Yang, Xinhua Chen, Jin Liu

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 1459 - 1470

Published: Jan. 1, 2025

The prevalence of osteoarthritis (OA), the most common chronic joint condition, is increasing due to aging population and escalating obesity rates, leading a significant impact on human health well-being. Thus, analyzing key targets OA through bioinformatics can help discover new biomarkers improve its diagnosis. microarray RNA-seq results were screened from Gene Expression Omnibus (GEO) database. Functional enrichment analyses, protein-protein interaction (PPI) analysis, weighted gene co-expression network analysis (WGCNA) DEGs performed. RT-qPCR WB further performed verify hub expression in rat. In this study, 35 genes identified differential using GSE169077 GSE114007 datasets. Enrichment revealed that these predominantly enriched HIF-1 signaling pathway, ECM-receptor interaction, FoxO pathway. Through integration validation animal models ROC curve four pivotal (GADD45B, CLDN5, HILPDA CDKN1B) finally identified. conclusion, could serve as novel for predicting treating OA, offering fresh insights into etiology pathogenesis.

Language: Английский

Citations

0
IGF2 secreted from mesenchymal stem cells with high glutathione levels alleviates osteoarthritis via paracrine rejuvenation of senescent chondrocytes DOI Creative Commons
Gun Hee Cho, Hyun Cheol Bae, Yu Jeong Lee

et al.

Biomaterials Research, Journal Year: 2025, Volume and Issue: 29

Published: Jan. 1, 2025

Senescent chondrocytes, which are increased in osteoarthritic (OA) cartilage, promote cartilage defects and the senescent knee microenvironment by inducing senescence to surrounding normal chondrocytes secreting senescence-associated secretory proteins. Many studies have used mesenchymal stem cells (MSCs) treat OA, but MSC treatment remains challenging for clinical application owing quality control, engraftment, fibrocartilage regeneration. Here, rather than relying on direct regeneration of MSCs, we present a novel strategy suppress OA MSC-mediated chondrocyte targeting via paracrine activity thereby improving microenvironment. First, enable control umbilical cord priming MSCs supplementing human platelet lysate (hPL) greatly enhanced functions increasing cellular glutathione levels throughout serial passaging. Intra-articular injection primed successfully suppressed progression accumulation without Indirect coculture with using transwell ameliorated phenotypes suggesting rejuvenation. Based secretome analysis, identified insulin-like growth factor 2 (IGF2) as key component that induces rejuvenation MSCs. The effects IGF2 act through autophagy activation up-regulation autophagy-related gene expression autophagic flux. To cross-validate secreted vivo, knockdown substantially abolished its therapeutic efficacy rabbit model. Collectively, these findings demonstrate hPL supplementation enables levels. mechanism was IGF2, activating autophagy.

Language: Английский

Citations

0