Inflammation Intensity-Dependent Expression of Osteoinductive Wnt Proteins Is Critical for Ectopic New Bone Formation in Ankylosing Spondylitis

Arthritis & Rheumatology
Xiang LiHui Liu

Abstract

To investigate the molecular mechanism underlying inflammation-related ectopic new bone formation in ankylosing spondylitis (AS). Spinal tissues and sera were collected from patients with AS and healthy volunteers and examined for the expression of Wnt proteins. An in vitro cell culture system mimicking the local inflammatory microenvironment of bone-forming sites was established to study the relationship between inflammation and Wnt expression, the regulatory mechanism of inflammation-induced Wnt expression, and the role of Wnt signaling in new bone formation. Modified collagen-induced arthritis (CIA) and proteoglycan-induced spondylitis (PGIS) animal models were used to confirm the key findings in vivo. The levels of osteoinductive Wnt proteins were increased in sera and spinal ligament tissues from patients with AS. Constitutive low-intensity tumor necrosis factor (TNF) stimulation, but not short-term or high-intensity TNF stimulation, induced persistent expression of osteoinductive Wnt proteins and subsequent bone formation through NF-κB (p65) and JNK/activator protein 1 (c-Jun) signaling pathways. Furthermore, inhibition of either the Wnt/β-catenin or Wnt/protein kinase Cδ (PKCδ) pathway significantly suppressed new bone f...Continue Reading

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Citations

Oct 9, 2019·Journal of Biochemical and Molecular Toxicology·Dongmei MaoQi Zhang
Jun 20, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiang LiHui Liu
Mar 23, 2018·Nature Reviews. Rheumatology·Joanna Collison
Jun 6, 2019·Arthritis Research & Therapy·Daniel E Furst, James S Louie
Nov 30, 2020·BMC Musculoskeletal Disorders·Christian S ThudiumMorten A Karsdal
Nov 27, 2020·Therapeutic Advances in Musculoskeletal Disease·Gavin Clunie, Nicole Horwood
Mar 16, 2021·Seminars in Immunopathology·Christopher Ritchlin
Aug 4, 2020·Journal of Translational Autoimmunity·Francesca MottaMatteo Vecellio
Jun 29, 2021·Frontiers in Endocrinology·Shunye ZhuZhenhua Yu

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