Constitutively activated NLRP3 inflammasome causes inflammation and abnormal skeletal development in mice.

PloS One
Sheri L BonarGabriel Mbalaviele

Abstract

The NLRP3 inflammasome complex is responsible for maturation of the pro-inflammatory cytokine, IL-1β. Mutations in NLRP3 are responsible for the cryopyrinopathies, a spectrum of conditions including neonatal-onset multisystem inflammatory disease (NOMID). While excessive production of IL-1β and systemic inflammation are common to all cryopyrinopathy disorders, skeletal abnormalities, prominently in the knees, and low bone mass are unique features of patients with NOMID. To gain insights into the mechanisms underlying skeletal abnormalities in NOMID, we generated knock-in mice globally expressing the D301N NLRP3 mutation (ortholog of D303N in human NLRP3). NOMID mice exhibit neutrophilia in blood and many tissues, including knee joints, and high levels of serum inflammatory mediators. They also exhibit growth retardation and severe postnatal osteopenia stemming at least in part from abnormally accelerated bone resorption, attended by increased osteoclastogenesis. Histologic analysis of knee joints revealed abnormal growth plates, with loss of chondrocytes and growth arrest in the central region of the epiphyses. Most strikingly, a tissue "spike" was observed in the mid-region of the growth plate in the long bones of all NOMID mi...Continue Reading

References

Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·R PacificiW A Peck
May 16, 2003·Nature·Henry M Kronenberg
Dec 3, 2005·The Journal of Clinical Investigation·Lawrence G Raisz
Jan 13, 2006·Nature·Fabio MartinonJürg Tschopp
Jan 13, 2006·Nature·Sanjeev MariathasanVishva M Dixit
Feb 28, 2006·The Journal of Pharmacology and Experimental Therapeutics·Gabriel MbalavieleJoseph Monahan
Dec 1, 2006·Pediatric Radiology·Suvimol Chirathivat HillRaphaela Goldbach-Mansky
Apr 26, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Alice Fiona Ford-HutchinsonFrank Robert Jirik
Jul 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jochen ZwerinaGeorg Schett
Nov 28, 2007·Annual Review of Pathology·Deborah V Novack, Steven L Teitelbaum
Mar 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sergio VairaDeborah Veis Novack
May 10, 2008·The Journal of Clinical Investigation·Sergio VairaDeborah Veis Novack
Jan 16, 2010·Science·Kate SchroderJurg Tschopp
Mar 3, 2010·Immunological Reviews·Nicole C Walsh, Ellen M Gravallese
Mar 23, 2010·Cell·Kate Schroder, Jurg Tschopp
Jul 8, 2010·Journal of Cell Science·Adriana Di BenedettoRoberto Civitelli
Feb 8, 2011·The Journal of Biological Chemistry·Hal M Hoffman, Susannah D Brydges
Feb 19, 2011·Journal of Leukocyte Biology·Taylor A DohertyHal M Hoffman
Feb 25, 2011·Molecular Biology of the Cell·Marcus WatkinsRoberto Civitelli
Sep 8, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Akinori MutoNaoyuki Takahashi
Mar 5, 2016·Molecular Neurodegeneration·Marina SaresellaMario Clerici

❮ Previous
Next ❯

Citations

Feb 16, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Michael C Heymann, Angela Rösen-Wolff
Sep 26, 2013·European Journal of Human Genetics : EJHG·Hermine A van DuyvenvoordeJan M Wit
Oct 6, 2014·Archives of Biochemistry and Biophysics·Alfredo CapparielloAnna Teti
May 15, 2013·Nature Reviews. Rheumatology·Alexander SoNathalie Busso
Aug 21, 2013·Nature Reviews. Gastroenterology & Hepatology·Alexander WreeAriel E Feldstein
Feb 18, 2016·Scientific Reports·Agnieszka RobaszkiewiczMichael O Hottiger
Sep 6, 2013·Immunological Investigations·Pedro P C Souza, Ulf H Lerner
Jul 3, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alexander WreeAriel E Feldstein
Apr 17, 2015·Immunological Reviews·Emily L Goldberg, Vishwa Deep Dixit
Apr 22, 2015·Seminars in Immunopathology·Pedro H V SaavedraMohamed Lamkanfi
Mar 10, 2015·Cellular and Molecular Life Sciences : CMLS·L Bessueille, D Magne
Dec 20, 2014·Cardiovascular Research·Stefano ToldoAntonio Abbate
Feb 9, 2017·Biochemical and Biophysical Research Communications·Linghao WangZhaohui Mo
Dec 16, 2016·Cell Reports·John N SnouwaertBeverly H Koller
Oct 3, 2017·Rheumatology·Brigitte Bader-MeunierCarine Wouters
Aug 30, 2017·Proceedings of the National Academy of Sciences of the United States of America·Hiroshi NakanishiAndrew J Griffith
Dec 19, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Juan Francisco Rodríguez-AlcázarBernardo S Franklin
Feb 19, 2015·Nature Communications·Kate E LawlorJames E Vince
Feb 12, 2019·British Journal of Pharmacology·Sohaib NizamiElena Di Daniel
Jan 13, 2018·Nature Reviews. Rheumatology·Matthew C WalshYongwon Choi
Jan 10, 2019·Journal of Clinical Periodontology·Reinhard Gruber
Dec 6, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chao QuGabriel Mbalaviele
Feb 18, 2015·Current Osteoporosis Reports·Michael R ConventeEileen M Shore
Sep 15, 2019·Seminars in Immunopathology·Yael Alippe, Gabriel Mbalaviele
Mar 20, 2018·The Journal of Experimental Medicine·Chun WangGabriel Mbalaviele
Sep 7, 2018·Clinical Science·Fiona Moghaddas, Seth L Masters
Jun 2, 2017·The Journal of Clinical Investigation·Gabriel MbalavieleSteven L Teitelbaum
Jul 28, 2017·Scientific Reports·Yael AlippeGabriel Mbalaviele
May 12, 2019·Journal of Clinical Immunology·Laela M Booshehri, Hal M Hoffman
Oct 15, 2019·Journal of Leukocyte Biology·Sarang Tartey, Thirumala-Devi Kanneganti
Jul 2, 2020·Cells·Maria Sebastian-Valverde, Giulio M Pasinetti
Sep 18, 2018·Oncoimmunology·Fernando ArandaLaura Senovilla
Dec 16, 2020·Journal of Cellular Physiology·L DetzenM Gosset
Feb 2, 2021·Science Advances·José M Navarro-PandoMario D Cordero

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Methods Mentioned

BETA
X-ray
FACS
biopsy
PCR
genotyping
ELISA
light microscopy
Infrared Imaging

Software Mentioned

FlowJo

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