SRY
Sex-determining region Y protein (Testis-determining factor) [TDF]
Publications[править]
The vestibular system of the inner ear contains Type I and Type II hair cells (HCs) generated from sensory progenitor cells; however, little is known about how the HC subtypes are formed. Sox2 (encoding SRY-box 2) is expressed in Type II, but not in Type I, HCs. The present study aimed to investigate the role of SOX2 in cell fate determination in Type I vs. Type II HCs. First, we confirmed that Type I HCs developed from Sox2-expressing cells through lineage tracing of Sox2-positive cells using a CAG-tdTomato reporter mouse crossed with a Sox2-CreER mouse. Then, Sox2 loss of function was induced in HCs, using Sox2 transgenic mice crossed with a Gfi1-Cre driver mouse. Knockout of Sox2 in HCs increased the number of Type I HCs and decreased the number of Type II HCs, while the total number of HCs and Sox2-positive supporting cells did not change. In addition, the effect of Sox2-knockout persisted into adulthood, resulting in an increased number of Type I HCs. These results demonstrate that SOX2 plays a critical role in the determination of Type II vs. Type I HC fate. The results suggested that Sox2 is a potential target for generating Type I HCs, which may be important for regenerative strategies for balance disorders.
MeSH Terms
- Aging
- Animals
- Cell Count
- Cell Differentiation
- Cell Lineage
- Hair Cells, Vestibular
- Mice
- Mice, Knockout
- Mice, Transgenic
- SOXB1 Transcription Factors
- Saccule and Utricle
Keywords
- SOX2
- balance disorder
- hair cell
- utricle
- vestibule
During the aging process, impaired osteoblastic function is one key factor of imbalanced bone formation and age-related bone loss. The aim of this study is to explore the differentially expressed genes in normal and aged osteoblasts and to identify genes potentially involved in age-related alteration in bone physiology. Based on next generation sequencing and bioinformatics analysis, 12 differentially expressed microRNAs and 22 differentially expressed genes were identified. Up-regulation of miR-204-5p was validated in an array of osteoporotic hip fracture in the Gene Expression Omnibus database (GSE74209). The putative targets for miR-204-5p were Kruppel-like factor 7 ([i]KLF7[/i]) and SRY-box 11 ([i]SOX11[/i]). Ingenuity Pathway Analysis identified [i]SOX11[/i], involved in osteoarthritis pathway and differentiation of osteoblasts, together with miR-204-5p, a potential upstream regulator, suggesting the critical role of miR-204-5p-[i]SOX11[/i] regulation in the aging process of human bones. In addition, as semaphorin 3A ([i]SEMA3A[/i]) and ephrin type-A receptor 5 ([i]EPHA5[/i]) were involved in nervous system related biological functions, we postulated a potential linkage between [i]SEMA3A[/i], [i]EPHA5[/i] and development of neurogenic heterotopic ossification. Our findings implicate new candidate genes in the diagnosis of geriatric musculoskeletal disorders, and provide novel insights that may contribute to the elaboration of new biomarkers for neurogenic heterotopic ossification.
Keywords
- aging osteoblasts
- bioinformatics
- messenger RNA
- microRNA
- next-generation sequencing
Adult articular chondrocytes undergo slow senescence and dedifferentiation during in vitro expansion, restricting successful cartilage regeneration. A complete understanding of the molecular signaling pathways involved in the senescence and dedifferentiation of chondrocytes is essential in order to better characterize chondrocytes for cartilage tissue engineering applications. During expansion, cell fate is determined by the change in expression of various genes in response to aspects of the microenvironment, including oxidative stress, mechanical stress, and unsuitable culture conditions. Rapid senescence or dedifferentiation not only results in the loss of the chondrocytic phenotype but also enhances production of inflammatory mediators and matrix-degrading enzymes. This review focuses on the two groups of genes that play direct and indirect roles in the induction of senescence and dedifferentiation. Numerous degenerative signaling pathways associated with these genes have been reported. Upregulation of the genes interleukin 1 beta (IL-1β), p53, p16, p21, and p38 mitogen-activated protein kinase (MAPK) is responsible for the direct induction of senescence, whereas downregulation of the genes transforming growth factor-beta (TGF-β), bone morphogenetic protein-2 (BMP-2), SRY (sex determining region Y)-box 9 (SOX9), and insulin-like growth factor-1 (IGF-1), indirectly induces senescence. In senescent and dedifferentiated chondrocytes, it was found that TGF-β, BMP-2, SOX9, and IGF-1 are downregulated, while the levels of IL-1β, p53, p16, p21, and p38 MAPK are upregulated followed by inhibition of the normal molecular functioning of the chondrocytes. This review helps to elucidate the underlying mechanism in degenerative cartilage disease, which may help to improve cartilage tissue regeneration techniques.
MeSH Terms
- Animals
- Bone Morphogenetic Protein 2
- Cartilage, Articular
- Cell Dedifferentiation
- Cellular Senescence
- Chondrocytes
- Cyclin-Dependent Kinase Inhibitor p21
- Gene Expression Regulation
- Genes, p16
- Genes, p53
- Guided Tissue Regeneration
- Humans
- In Vitro Techniques
- Insulin-Like Growth Factor I
- Interleukin-1beta
- SOX9 Transcription Factor
- Signal Transduction
- Transforming Growth Factor beta
- Up-Regulation
- p38 Mitogen-Activated Protein Kinases
Keywords
- Cartilage
- Chondrocytes
- Dedifferentiation
- Genes
- Senescence