2016
DOI: 10.1016/j.joca.2015.07.008
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Regulation of senescence associated signaling mechanisms in chondrocytes for cartilage tissue regeneration

Abstract: 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, … Show more

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Cited by 155 publications
(128 citation statements)
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“…The utility of p16 INK4a as a biomarker of molecular age in other cell types has been demonstrated by assessing the impact of lifestyle modifications such as smoking or exercise (Liu et al., 2009), predicting the risk for particular negative outcomes after chemotherapy (Demaria et al., 2017), and screening the quality of potential donor organs (Koppelstaetter et al., 2008). For chondrocytes, screening patients for low p16 INK4a expression may improve the outcomes of autologous chondrocyte implantation procedures, as the success of this procedure requires avoidance of senescence to ensure sufficient expansion and subsequent re‐differentiation of the chondrocytes (Ashraf et al., 2016). …”
Section: Discussionmentioning
confidence: 99%
“…The utility of p16 INK4a as a biomarker of molecular age in other cell types has been demonstrated by assessing the impact of lifestyle modifications such as smoking or exercise (Liu et al., 2009), predicting the risk for particular negative outcomes after chemotherapy (Demaria et al., 2017), and screening the quality of potential donor organs (Koppelstaetter et al., 2008). For chondrocytes, screening patients for low p16 INK4a expression may improve the outcomes of autologous chondrocyte implantation procedures, as the success of this procedure requires avoidance of senescence to ensure sufficient expansion and subsequent re‐differentiation of the chondrocytes (Ashraf et al., 2016). …”
Section: Discussionmentioning
confidence: 99%
“…Although their competence for proliferation indicates that these chondrocytes are not senescent, cells that enter the cell cycle in the context of potentially damaging stimuli have an increased likelihood of entering senescence as opposed to returning to quiescence 53,54 . Observations that senescence occurs after monolayer expansion of chondrocytes (reviewed elsewhere 55 ) provide further evidence that contexts of increased proliferation correlate with emergence of the senescent phenotype.…”
Section: Cellular Senescence and The Saspmentioning
confidence: 92%
“…In addition, senescent cells show altered intracellular protein expression, altered responses to growth factors, and altered secretion profiles such as elevated levels of ROS and pro-inflammatory cytokine production, which contribute further to overall aging and progression of age-related diseases (Loeser 2009, Ashraf et al. 2016). …”
Section: Aging and Cellular Senescencementioning
confidence: 99%