Wiley
0892-6638
1530-6860
Cơ quản chủ quản: John Wiley & Sons Inc. , WILEY
Lĩnh vực:
BiochemistryMedicine (miscellaneous)GeneticsBiotechnologyMolecular Biology
Phân tích ảnh hưởng
Thông tin về tạp chí
Các bài báo tiêu biểu
Controlled induction and targeted elimination of p16<sup>INK4a</sup>‐expressing chondrocytes in cartilage explant culture Cellular senescence is a phenotypic state that contributes to age‐related diseases through the secretion of matrix‐degrading and inflammatory molecules. An emerging therapeutic strategy for osteoarthritis (OA) is to selectively eliminate senescent cells by initiating apoptosis. This study establishes a cartilage explant model of senescence induction and senolytic clearance using p16Ink4a expression as a biomarker of senescence. Growth‐factor stimulation of explants increased the expression of p16Ink4a at both the mRNA and protein levels. Applying this culture system to cartilage from p16tdTom reporter mice (a knockin allele with tdTomato fluorescent protein regulated by the endogenous p16Ink4a promoter) demonstrated the emergence of a p16‐high population that was quantified using flow cytometry for tdTomato. Cell sorting was used to separate chondrocytes based on tdTomato fluorescence and p16‐high cells showed higher senescence‐associated β‐galactosidase activity and increased gene expression of the senescence‐associated secretory phenotype as compared with p16‐low cells. The potential for effective senolysis within the cartilage extracellular matrix was assessed using navitoclax (ABT‐263). Navitoclax treatment reduced the percentage of p16‐high cells from 17.9 to 6.1% (mean of 13 matched pairs; P < 0.001) and increased cleaved caspase‐3 confirmed apoptotic activity. Together, these findings establish a physiologically relevant cartilage explant model for testing the induction and elimination of senescent chondrocytes, which will support investigations of senolytic therapy for OA.—Sessions, G. A., Copp, M. E., Liu, J.‐Y., Sinkler, M. A., D'Costa, S., Diekman, B. O. Controlled induction and targeted elimination of p16INK4a ‐expressing chondrocytes in cartilage explant culture. FASEB J. 33, 12364–12373 (2019). www.fasebj.org
Tập 33 Số 11 - Trang 12364-12373 - 2019
New insights on mammalian phospholipase A <sub>2</sub> (s); comparison of arachidonoyl‐selective and ‐nonselective enzymes
Tập 7 Số 2 - Trang 339-348 - 1993
Interaction of low molecular weight group IIA phospholipase A<sub>2</sub>with apoptotic human T cells: role of heparan sulfate proteoglycans
Tập 17 Số 9 - Trang 1068-1080 - 2003
Binding inhibition of angiogenic factors by heparan sulfate proteoglycans in aqueous humor: potential mechanism for maintenance of an avascular environment
Tập 17 Số 8 - Trang 1-20 - 2003
MicroRNAs in resolution of acute inflammation: identification of novel resolvin Dl‐miRNA circuits
Tập 25 Số 2 - Trang 544-560 - 2011
Expression of <i>Cyp2c/Cyp2j</i> subfamily members and oxylipin levels during LPS‐induced inflammation and resolution in mice Inflammatory stimuli, such as bacterial LPS, alter the expression of many cytochromes P450. CYP2C and CYP2J subfamily members actively metabolize fatty acids to bioactive eicosanoids, which exhibit potent anti‐inflammatory effects. Herein, we examined mRNA levels of the 15 mouse Cyp2c and 7 mouse Cyp2j isoforms in liver, kidney, duodenum, and brain over a 96‐h time course of LPS‐induced inflammation and resolution. Plasma and liver eicosanoid levels were also measured by liquid chromatography with tandem mass spectrometry. Expression changes in Cyp2c and Cyp2j isoforms were both isoform and tissue specific. Total liver Cyp2c and Cyp2j mRNA content was reduced by 80% 24 h after LPS but recovered to baseline levels by 96 h. Total Cyp2c and Cyp2j mRNA in kidney (‐19%) and duodenum (‐64%) were reduced 24 h after LPS but recovered above baseline by 72 h. Total Cyp2c and Cyp2j mRNA content in brain was elevated at all time points after LPS dosing. Plasma eicosanoids transiently increased 3‐6 h after administration of LPS. In liver, esterified oxylipin levels decreased during acute inflammation and before recovering. The biphasic suppression and recovery of mouse Cyp2c and Cyp2j isoforms and associated changes in eicosanoid levels during LPS‐induced inflammation and resolution may have important physiologic consequences.—Graves, J. P., Bradbury, J. A., Gruzdev, A., Li, H., Duval, C., Lih, F. B., Edin, M. L., Zeldin, D. C. Expression of Cyp2c/Cyp2j subfamily members and oxylipin levels during LPS‐induced inflammation and resolution in mice. FASEB J. 33, 14784‐14797 (2019). www.fasebj.org
Tập 33 Số 12 - Trang 14784-14797 - 2019
Galectin‐4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function
Tập 30 Số 2 - Trang 544-554 - 2016
Activated mineralocorticoid receptor regulates micro‐RNA‐29b in vascular smooth muscle cells
Tập 30 Số 4 - Trang 1610-1622 - 2016
Cell‐autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis
Tập 19 Số 8 - Trang 1027-1029 - 2005
Up‐regulation of microRNA‐142 in simian immunodeficiency virus encephalitis leads to repression of sirtuin1
Tập 27 Số 9 - Trang 3720-3729 - 2013