SOX9+ enthesis cells are associated with spinal ankylosis in ankylosing spondylitis.
Osteoarthritis Cartilage
; 30(2): 280-290, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-34826571
ABSTRACT
OBJECTIVE:
Although cartilage degeneration and invasion of the subchondral bone plate in entheseal lesion has been considered to consequently lead bony ankylosis in ankylosing spondylitis (AS), no evident mechanisms are known.DESIGN:
To identify histopathological and physiological changes in enthesitis-related ankylosis in AS, we performed molecular characterization of transcription factors and surface markers, and transcriptome analysis with human tissues. Entheseal tissue containing subchondral bone was obtained from the facet joints of 9 patients with AS and 10 disease controls, and assessed by using differential staining techniques. Enthesis cells were isolated, characterized, stimulated with TNF and/or IL-17A, and analysed by cell-based experimental tools.RESULTS:
We found diffusely distributed granular tissue and cartilage in the subchondral bone in AS. Co-expression of SOX9, a specific transcription factor in cartilage, and matrix metalloproteinase 13 (MMP13) was found in the granular tissues within the subchondral bone from AS patients. Intriguingly, SOX9 expression was significantly higher in AS enthesis cells than controls and correlated with TNFR1 and IL-17RA expressions, which is important for high reactivity to TNF and IL-17A cytokines. Co-stimulation by TNF and IL-17A resulted in accelerated mineralization/calcification features, and increased OCN expression in AS enthesis cells. Furthermore, SOX9 overexpression in enthesis leads to promoting mineralization feature by TNF and IL-17A stimuli. Finally, OCN expression is elevated in the destructive enthesis of advanced AS.CONCLUSION:
These findings provide insight into the links between inflammation and the mineralization of entheseal tissue as the initiation of spinal ankylosis, emphasizing the importance of SOX9+ enthesis cells.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spinal Diseases
/
Spondylitis, Ankylosing
/
SOX9 Transcription Factor
/
Ankylosis
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Osteoarthritis Cartilage
Journal subject:
ORTOPEDIA
/
REUMATOLOGIA
Year:
2022
Document type:
Article
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM