Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts

Cota, Perla; Helmi, Summer A.; Hsu, Charlie Yu Ming; Rancourt, Derrick E.

doi:10.3390/cells9010191

Cited by 7 publications

(3 citation statements)

References 40 publications

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“…Therefore, effectively reducing cancer risk still requires ongoing efforts. Cota et al proposed a new viewpoint that in terms of speedier reprogramming of the required cells, transdifferentiation of a completely differentiated cell state directly into another differentiated cell state avoids the drawbacks of fully reprogramming cells to iPSCs ( Cota et al, 2020 ). By bypassing the iPSC stage, transdifferentiation also decreases the chance of tumor formation ( Cota et al, 2020 ).…”

Section: Cancer Riskmentioning

confidence: 99%

The occurrence and development of induced pluripotent stem cells

Chen,

Li,

2024

Front. Genet.

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The ectopic expression of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc (OSKM), known as “Yamanaka factors,” can reprogram or stimulate the production of induced pluripotent stem cells (iPSCs). Although OSKM is still the gold standard, there are multiple ways to reprogram cells into iPSCs. In recent years, significant progress has been made in improving the efficiency of this technology. Ten years after the first report was published, human pluripotent stem cells have gradually been applied in clinical settings, including disease modeling, cell therapy, new drug development, and cell derivation. Here, we provide a review of the discovery of iPSCs and their applications in disease and development.

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Section: Cancer Riskmentioning

confidence: 99%

The occurrence and development of induced pluripotent stem cells

Chen,

Li,

2024

Front. Genet.

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“…This mechanism is a lineage conversion or direct cell reprogramming process that uses lineage-specific transcription factors to change a differentiated cell type into another cell fate and avoid forming a pluripotent state. An alternative method of transdifferentiation combines directed differentiation and partial reprogramming [ 41 , 54 ]. In this regard, instead of a tumor driving process, trans-differentiation can be considered a tool to encounter cancer cells more gently and convert them to a more benign or at least more sensitive and less aggressive type.…”

Section: Cancer-ipscs and Other Pscs: A Comparison Studymentioning

confidence: 99%

Cancer cells as a new source of induced pluripotent stem cells

et al. 2022

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Over the last 2 decades, induced pluripotent stem cells (iPSCs) have had various potential applications in various medical research areas, from personalized medicine to disease treatment. Different cellular resources are accessible for iPSC generation, such as keratinocytes, skin fibroblasts, and blood or urine cells. However, all these sources are somatic cells, and we must make several changes in a somatic cell’s transcriptome and chromatin state to become a pluripotent cell. It has recently been revealed that cancer cells can be a new source of iPSCs production. Cancer cells show similarities with iPSCs in self-renewal capacity, reprogramming potency, and signaling pathways. Although genetic abnormalities and potential tumor formation in cancer cells pose a severe risk, reprogrammed cancer-induced pluripotent stem cells (cancer-iPSCs) indicate that pluripotency can transiently overcome the cancer phenotype. This review discusses whether cancer cells can be a preferable source to generate iPSCs.

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“…JAKs are tyrosine kinases associated with cytoplasmic receptors and are the first signaling pathways involved in cytokine stimulation [ 14 ]. So far, four members of the JAK family have been identified: JAK1, JAK2, JAK3, and Tyk2.…”

Section: Introductionmentioning

confidence: 99%

GSK3B Overexpression Alleviates Posttraumatic Osteoarthritis in Mice by Promoting DNMT1-Mediated Hypermethylation of NR4A3 Promoter

Sun

et al. 2022

Disease Markers

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Background. Glycogen synthase kinase 3β (GSK3B) is reported to be a protective factor for the degradation of chondrocytes by extracellular mechanisms. Nuclear receptor subfamily 4 group A member 3 (NR4A3) is a proinflammatory factor in osteoarthritis. Their regulation mechanism in posttraumatic osteoarthritis (PTOA) is not fully understood. Methods. GSK3B expression in the cartilage tissue of PTOA patients was analyzed by western blotting. IL-1β-induced chondrocytes were transfected with pcDNA-GSK3B, and then, the cell viability, apoptosis, expression of the chondrocyte extracellular matrix degradation-related genes MMP13, aggrecan, and type II collagen, and secretion of inflammatory factors TNF-α and IL-6 were detected. Co-IP was used to analyze the interaction between GSK3B and DNMT1. Ch-IP and methylation-specific PCR assays were used for methylation. Also, cells were transfected with pcDNA-GSK3B or together with pcDNA-NR4A3, as well as transfected with si-NR4A3, and then, cell functions were tested. Then, the mice subjected to destabilization of medial meniscus (DMM) surgery were intra-articular injected with 100 μL of the following adeno-related virus vectors (empty vector, Ad-GSK3B, scrambled shRNA, and sh-NR4A3), respectively, and the virus titer was 2 × 10 8 TU / mL . Cartilage integrity was evaluated by safranin O/fast green staining, HE staining, and Osteoarthritis Research Society International (OARSI) score. Results. The expression of GSK3B protein was downregulated in PTOA patients. GSK3B overexpression alleviated IL-1β-induced chondrocyte apoptosis and extracellular matrix degradation, as well as cartilage mineralization in PTOA model mice. NR4A3 overexpression reversed the effect of GSK3B on IL-1β-induced chondrocyte functions. GSK3B could recruit DNMT1 to the NR4A3 promoter region to promote the methylation of NR4A3 and inhibit the expression of NR4A3 protein. Similarly, NR4A3 interference alleviated cartilage degradation under stimulating conditions by inhibiting the activation of the JAK2/STAT3 signaling pathway. Conclusion. GSK3B recruits DNMT1 to the NR4A3 promoter region and inhibits the activation of the NR4A3-mediated JAK2/STAT3 signaling pathway, thereby alleviating PTOA.

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Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts

Cited by 7 publications

References 40 publications

The occurrence and development of induced pluripotent stem cells

The occurrence and development of induced pluripotent stem cells

Cancer cells as a new source of induced pluripotent stem cells

GSK3B Overexpression Alleviates Posttraumatic Osteoarthritis in Mice by Promoting DNMT1-Mediated Hypermethylation of NR4A3 Promoter

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