New Insights for RANKL as a Proinflammatory Modulator in Modeled Inflammatory Arthritis

Frontiers in Immunology
Maria PapadakiEleni Douni

Abstract

Receptor activator of nuclear factor-κB ligand (RANKL), a member of the Tumor Necrosis Factor (TNF) superfamily, constitutes the master regulator of osteoclast formation and bone resorption, whereas its involvement in inflammatory diseases remains unclear. Here, we used the human TNF transgenic mouse model of erosive inflammatory arthritis to determine if the progression of inflammation is affected by either genetic inactivation or overexpression of RANKL in transgenic mouse models. TNF-mediated inflammatory arthritis was significantly attenuated in the absence of functional RANKL. Notably, TNF overexpression could not compensate for RANKL-mediated osteopetrosis, but promoted osteoclastogenesis between the pannus and bone interface, suggesting RANKL-independent mechanisms of osteoclastogenesis in inflamed joints. On the other hand, simultaneous overexpression of RANKL and TNF in double transgenic mice accelerated disease onset and led to severe arthritis characterized by significantly elevated clinical and histological scores as shown by aggressive pannus formation, extended bone resorption, and massive accumulation of inflammatory cells, mainly of myeloid origin. RANKL and TNF cooperated not only in local bone loss identified ...Continue Reading

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Citations

Jan 17, 2020·Human Molecular Genetics·Dounia HamoudiJérôme Frenette
Mar 12, 2020·International Journal of Molecular Sciences·Jessica DörnenThomas Dittmar
Aug 20, 2020·The Journal of Pharmacy and Pharmacology·Shareen SinghSonia Dhiman
Apr 3, 2020·International Journal of Molecular Medicine·Elisa TorreNazario Russo
Jun 11, 2020·Pediatric Rheumatology Online Journal·Emily J LieblingEdward M Behrens
Oct 20, 2020·The Journal of Experimental Medicine·Begüm AlankusJürgen Ruland
Jun 15, 2021·Frontiers in Pharmacology·Shahin ShamsJudith F Ashouri
Aug 25, 2021·Expert Review of Clinical Immunology·Ana Lleo, M Eric Gershwin
Jul 17, 2021·Tissue Engineering. Part a·Nolutho MkhumbeniKeolebogile Shirley Caroline Motaung

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Methods Mentioned

BETA
transgenic
FACS
PCR
acetylation
flow cytometry

Software Mentioned

Xcalibur
FlowJo
TrapHisto
Andromeda
NRecon
Perseus
Cytoscape
CluePedia
ClueGO
MaxQuant

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