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==Publications== {{medline-entry |title=The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32727592 |abstract=Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear. In this study, we compared PDLSCs isolated from young and adult individuals. PDLSC proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSC osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining, and related quantitative analysis. PDLSC immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs. Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation of [[CCND3]] and [[RC3H2]], and a downregulation of Runx2, ALP, [[COL1A1]], PPARγ2, [[CXCL12]], [[FKBP1A]], [[FKBP1B]], [[NCSTN]], [[P2RX7]], [[PPP3CB]], [[RIPK2]], [[SLC11A1]], and [[TP53]] in those from adult individuals. Furthermore, protein expression levels of Runx2, ALP, [[COL1A1]], and PPARγ2 in the adult group were decreased, whereas that of [[CCND3]] increased. Taken together, aging influences the biological and immunological characteristics of PDLSCs, and thus, it is more appropriate to utilize PDLSCs from young individuals for tissue regeneration, post-aging treatment, and allotransplantation. |keywords=* Aging * Immunosuppression * Osteogenic differentiation * Periodontal ligament stem cells * Peripheral blood mononuclear cells * Tissue engineering |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392710 }} {{medline-entry |title=A rare functional haplotype of the [[P2RX4]] and [[P2RX7]] genes leads to loss of innate phagocytosis and confers increased risk of age-related macular degeneration. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23303206 |abstract=Age-related macular degeneration (AMD) is a leading cause of blindness in Western countries and is diagnosed by the clinical appearance of yellow subretinal deposits called drusen. Genetic changes in immune components are clearly implicated in the pathology of this disease. We have previously shown that the purinergic receptor P2X7 can act as a scavenger receptor, mediating phagocytosis of apoptotic cells and insoluble debris. We performed a genetic association study of functional polymorphisms in the [[P2RX7]] and [[P2RX4]] genes in a cohort of 744 patients with AMD and 557 age-matched Caucasian control subjects. The P2X4 Tyr315Cys variant was 2-fold more frequent in patients with AMD compared to control subjects, with the minor allele predicting susceptibility to disease. Pairwise linkage disequilibrium was observed between Tyr315Cys in the [[P2RX4]] gene and Gly150Arg in the [[P2RX7]] gene, and these two minor alleles formed a rare haplotype that was overrepresented in patients with AMD (n=17) compared with control subjects (n=3) (odds ratio 4.05, P=0.026). Expression of P2X7 (wild type or variant 150Arg) in HEK293 cells conferred robust phagocytosis toward latex beads, whereas coexpression of the P2X7 150Arg with P2X4 315Cys variants almost completely inhibited phagocytic capacity. Fresh human monocytes harboring this heterozygous 150Arg-315Cys haplotype showed 40% reduction in bead phagocytosis. In the primate eye, immunohistochemistry indicated that P2X7 and P2X4 receptors were coexpressed on microglia and macrophages, but neither receptor was seen on retinal pigment epithelial cells. These results demonstrate that a haplotype including two rare variants in [[P2RX7]] and [[P2RX4]] confers a functional interaction between these two variant receptors that impairs the normal scavenger function of macrophages and microglia. Failure of this P2X7-mediated phagocytic pathway may impair removal of subretinal deposits and predispose individuals toward AMD. |mesh-terms=* Aged * Aged, 80 and over * Aging * Alleles * European Continental Ancestry Group * Female * Genetic Association Studies * Genetic Predisposition to Disease * Genotype * Haplotypes * Humans * Linkage Disequilibrium * Macular Degeneration * Male * Middle Aged * Phagocytosis * Polymorphism, Single Nucleotide * Receptors, Purinergic P2X4 * Receptors, Purinergic P2X7 * Risk Factors |full-text-url=https://sci-hub.do/10.1096/fj.12-215368 }}
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