Preosteoclast plays a pathogenic role in syndesmophyte formation of ankylosing spondylitis through the secreted PDGFB - GRB2/ERK/RUNX2 pathway.
Ankylosing spondylitis
Osteogenesis
PDGFB
Syndesmophyte formation
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
05 10 2023
05 10 2023
Historique:
received:
14
11
2022
accepted:
21
08
2023
medline:
9
10
2023
pubmed:
6
10
2023
entrez:
5
10
2023
Statut:
epublish
Résumé
Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the sacroiliac joint and spine. However, the real mechanisms of immune cells acting on syndesmophyte formation in AS are not well identified. We aimed to find the key AS-associated cytokine and assess its pathogenic role in AS. A protein array with 1000 cytokines was performed in five AS patients with the first diagnosis and five age- and gender-matched healthy controls to discover the differentially expressed cytokines. The candidate differentially expressed cytokines were further quantified by multiplex protein quantitation (3 AS-associated cytokines and 3 PDGF-pathway cytokines) and ELISA (PDGFB) in independent samples (a total of 140 AS patients vs 140 healthy controls). The effects of PDGFB, the candidate cytokine, were examined by using adipose-derived stem cells (ADSCs) and human fetal osteoblast cell line (hFOB1.19) as in vitro mesenchymal cell and preosteoblast models, respectively. Furthermore, whole-transcriptome sequencing and enrichment of phosphorylated peptides were performed by using cell models to explore the underlying mechanisms of PDGFB. The xCELLigence system was applied to examine the proliferation, chemotaxis, and migration abilities of PDGFB-stimulated or PDGFB-unstimulated cells. The PDGF pathway was observed to have abnormal expression in the protein array, and PDGFB expression was further found to be up-regulated in 140 Chinese AS patients. Importantly, PDGFB expression was significantly correlated with BASFI (Pearson coefficient/p value = 0.62/6.70E - 8) and with the variance of the mSASSS score (mSASSS PDGFB stimulates the GRB2/ERK/RUNX2 pathway in ADSCs, promotes osteoblastogenesis of ADSCs, and enhances the extracellular matrix of osteoblasts, which may contribute to pathological bone formation in AS.
Identifiants
pubmed: 37798786
doi: 10.1186/s13075-023-03142-3
pii: 10.1186/s13075-023-03142-3
pmc: PMC10552372
doi:
Substances chimiques
Core Binding Factor Alpha 1 Subunit
0
Cytokines
0
GRB2 Adaptor Protein
0
GRB2 protein, human
0
Proto-Oncogene Proteins c-sis
0
RUNX2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
194Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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