Progranulin knockout accelerates intervertebral disc degeneration in aging mice

Scientific Reports
Yun-Peng ZhaoChuan-Ju Liu

Abstract

Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases.

References

Jan 14, 2003·Nature Medicine·Zhiheng HeAndrew Bateman
Jan 22, 2004·Journal of Spinal Disorders & Techniques·Sten HolmTommy Hansson
Nov 27, 2004·Spine·Jill P G UrbanJeremy C T Fairbank
Jul 15, 2005·Annals of the Rheumatic Diseases·S R PyeT W O'Neill
Oct 26, 2010·The Spine Journal : Official Journal of the North American Spine Society·Kenneth M C Cheung
Jun 8, 2011·Annals of the Rheumatic Diseases·Gregory LivshitsFrances M K Williams
Apr 11, 2012·Bone·Martin Lotz, Richard F Loeser
Jun 19, 2012·World Neurosurgery·W Mark Erwin, Michael G Fehlings
Oct 9, 2012·The Journal of Clinical Investigation·Lauren Herl MartensRobert V Farese
May 11, 2013·Arthritis and Rheumatism·Matthew R McCannCheryle A Séguin
Mar 19, 2014·Journal of Visualized Experiments : JoVE·Yunpeng ZhaoChuan-ju Liu
Aug 30, 2014·Annals of the Rheumatic Diseases·Yun-Peng ZhaoChuan-Ju Liu

❮ Previous
Next ❯

Citations

Feb 1, 2017·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Stefan DudliJeffrey C Lotz
Apr 28, 2019·International Journal of Molecular Sciences·Clara Ruiz-FernándezOreste Gualillo
Jul 17, 2018·Annals of the New York Academy of Sciences·Michal LataChuan-Ju Liu
Apr 28, 2018·Cytokine & Growth Factor Reviews·Yuehong ChenChuan-Ju Liu
Jul 27, 2021·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Yidian WangXuewen Kang

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
nuclear translocation
genotyping

Software Mentioned

OsteoMeasure
Statistical Package for Social Sciences

Related Concepts

Related Feeds

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.