Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease which can involve bone joint degradation. The Wnt-β/catenin signalling pathway is a major promoter of bone formation. Following triple-DMARD treatment of rheumatoid arthritis patients, systemic levels of sclerostin are increased, correlating with improved patient response. This lies in contrast with the established role of sclerostin as a Wnt-antagonist, which would inhibit bone formation and suggests a protective role for sclerostin against bone loss. However, it is not known if this change is reflected in synovial tissues, the site of inflammation in RA.
Objectives: This study characterised the expression of sclerostin and other biomarkers associated with bone metabolism in synovial tissue biopsy samples in relation to patient erosive status (Sharpe/van der Heijde method), the presence of TNF (as judged by immunohistochemistry (IHC)) and response to treatment (European League Against Rheumatism (EULAR) scores).
Methods: Arthroscopic synovial tissue biopsies from patients with early rheumatoid arthritis, before and after treatment with adalimumab or abatacept were examined for sclerostin and LRP5/6, by immunohistochemistry (IHC), immunofluorescence staining, flow cytometry and bulk RNA sequencing, in addition to other biomarkers associated with bone metabolism. Total RNA libraries were produced using the Tecan Universal Plus Total RNA library preparation kit. Samples were sequenced on 3 x S4 lanes of the NovaSeq using paired end 100 bp reads (Illumina).
Results: No significant changes were observed for both sclerostin and LRP5/6 between erosive and non-erosive patients and at 6-month post-treatment. However, the expression of sclerostin in IHC stains of synovial tissues was significantly increased in TNF-non-dominant patients compared to those who were TNF-dominant. Sclerostin and LRP5/6 expression was localised to different cell populations in synovial tissue.
Conclusion: Bulk assessment of sclerostin and other bone biomarkers within synovial tissue does not currently demonstrate a relationship with clinical outcome. However, further assessment of sclerostin and other biomarkers of bone activity in specific cell types, within synovial tissue, can provide further insights into the role of sclerostin and Wnt pathway molecules in bone homeostasis in the context of RA and may provide biomarkers of erosive disease progression.
Objectives: This study characterised the expression of sclerostin and other biomarkers associated with bone metabolism in synovial tissue biopsy samples in relation to patient erosive status (Sharpe/van der Heijde method), the presence of TNF (as judged by immunohistochemistry (IHC)) and response to treatment (European League Against Rheumatism (EULAR) scores).
Methods: Arthroscopic synovial tissue biopsies from patients with early rheumatoid arthritis, before and after treatment with adalimumab or abatacept were examined for sclerostin and LRP5/6, by immunohistochemistry (IHC), immunofluorescence staining, flow cytometry and bulk RNA sequencing, in addition to other biomarkers associated with bone metabolism. Total RNA libraries were produced using the Tecan Universal Plus Total RNA library preparation kit. Samples were sequenced on 3 x S4 lanes of the NovaSeq using paired end 100 bp reads (Illumina).
Results: No significant changes were observed for both sclerostin and LRP5/6 between erosive and non-erosive patients and at 6-month post-treatment. However, the expression of sclerostin in IHC stains of synovial tissues was significantly increased in TNF-non-dominant patients compared to those who were TNF-dominant. Sclerostin and LRP5/6 expression was localised to different cell populations in synovial tissue.
Conclusion: Bulk assessment of sclerostin and other bone biomarkers within synovial tissue does not currently demonstrate a relationship with clinical outcome. However, further assessment of sclerostin and other biomarkers of bone activity in specific cell types, within synovial tissue, can provide further insights into the role of sclerostin and Wnt pathway molecules in bone homeostasis in the context of RA and may provide biomarkers of erosive disease progression.
Original language | English |
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Pages (from-to) | 1206 |
Number of pages | 1 |
Journal | Annals of the Rheumatic Diseases |
Volume | 82 |
Issue number | S1 |
DOIs | |
Publication status | Published - Jun 2023 |
Event | European Congress of Rheumatology 2023 - Milan, Italy Duration: 31 May 2023 → 3 Jun 2023 |
Keywords
- Bone biomarkers
- Rheumatoid arthritis
- Synovial tissue
- Chronic autoimmune disease
- Bone-joint degradation