p16Ink4a deletion in cells of the intervertebral disc affects their matrix homeostasis and senescence associated secretory phenotype without altering onset of senescence

Matrix Biology : Journal of the International Society for Matrix Biology
Emanuel J NovaisM V Risbud

Abstract

Intervertebral disc degeneration is an important contributor to chronic low back and neck pain. Although many environmental and genetic factors are known to contribute to disc degeneration, age is still the most significant risk factor. Recent studies have shown that senescence may play a role in age-related disc degeneration and matrix catabolism in humans and mouse models. Clearance of p16Ink4a-positive senescent cells reduces the degenerative phenotype in many age-associated diseases. Whether p16Ink4a plays a functional role in intervertebral disc degeneration and senescence is unknown. We first characterized the senescence status of discs in young and old mice. Quantitative histology, gene expression and a novel p16tdTom reporter mice showed an increase in p16Ink4a, p21 and IL-6, with a decrease in Ki67 with aging. Accordingly, we studied the spinal-phenotype of 18-month-old mice with conditional deletion of p16Ink4a in the disc driven by Acan-CreERT2 (cKO). The analyses of discs of cKO and age-matched control mice showed little change in cell morphology and tissue architecture. The cKO mice exhibited changes in functional attributes of aggrecan as well as in collagen composition of the intervertebral disc. While cKO discs ...Continue Reading

Citations

Mar 16, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Deborah J GorthMakarand V Risbud
Nov 7, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Elizabeth S SilagiMakarand V Risbud
Aug 14, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Garrett A SessionsBrian O Diekman
Dec 5, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Deborah J GorthMakarand V Risbud
Sep 17, 2020·Oxidative Medicine and Cellular Longevity·Yuang ZhangQixin Chen
Aug 1, 2020·International Journal of Molecular Sciences·Grace Jean CampbellMathew Van de Pette
Oct 14, 2020·Scientific Reports·Hidetoshi SugiharaKeitaro Yamanouchi
Dec 11, 2020·Matrix Biology : Journal of the International Society for Matrix Biology·Vedavathi MadhuMakarand V Risbud
Apr 5, 2021·Biochemical and Biophysical Research Communications·Jiancheng ZhengLianfu Deng
May 1, 2021·Life·Kelly E LeonRaquel Buj
Aug 18, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sajjad AshrafRita Kandel

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