Two-year post-distraction cartilage-related structural improvement is accompanied by increased serum full-length SIRT1

• Published in: Arthritis research & therapy Vol. 26; no. 1; pp. 106 - 13
• Main Authors: Marco, Miya, Jansen, Mylène, van der Weiden, Goran, Reich, Eli, Maatuf, Yonathan H, Mastbergen, Simon C, Dvir-Ginzberg, Mona
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24-05-2024; BMC
• Subjects: Adult; Aged; Biological markers; Biomarkers - blood; Care and treatment; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Development and progression; ELISA; Endotype; Enzyme-Linked Immunosorbent Assay; Enzymes; Female; Full-length Sirt1; Genetic aspects; Health aspects; Humans; Hydrolases; Identification and classification; Joint distraction; Knee Joint - diagnostic imaging; Knee Joint - pathology; Longitudinal Studies; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Knee - blood; Osteoarthritis, Knee - surgery; Serum biomarker; Sirtuin 1 - blood; Netherlands; Serum biomarker; Endotype; Full-length Sirt1; Joint distraction; Osteoarthritis; ELISA
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-024-03342-5

Previously, fragments from Sirtuin 1 (SIRT1) were identified in preclinical and clinical samples to display an increase in serum levels for N-terminal (NT) SIRT1 vs. C-terminal (CT) SIRT1, indicative of early signs of OA. Here we tested NT/CT SIRT1 levels as well as a novel formulated sandwich assay to simultaneously detect both domains of SIRT1 in a manner that may inform us about the levels of full-length SIRT1 in the circulation (flSIRT1) of clinical cohorts undergoing knee joint distraction (KJD).
We employed an indirect ELISA assay to test NT- and CT-SIRT1 levels and calculated their ratio. Further, to test flSIRT1 we utilized novel antibodies (Ab), which were validated for site specificity and used in a sandwich ELISA method, wherein the CT-reactive served as capture Ab, and its NT-reactive served as primary detection Ab. This method was employed in human serum samples derived from a two-year longitudinal study of KJD patients. Two-year clinical and structural outcomes were correlated with serum levels of flSIRT1 compared to baseline.
Assessing the cohort, exhibited a significant increase of NT/CT SIRT1 serum levels with increased osteophytes and PIIANP/CTX-II at baseline, while a contradictory increase in NT/CT SIRT1 was associated with less denuded bone, post-KJD. On the other hand, flSIRT1 exhibited an upward trend in serum level, accompanied by reduced denuded bone for 2-year adjusted values. Moreover, 2 year-adjusted flSIRT1 levels displayed a steeper linear regression for cartilage and bone-related structural improvement than those observed for NT/CT SIRT1.
Our data support that increased flSIRT1 serum levels are a potential molecular endotype for cartilage-related structural improvement post-KJD, while NT/CT SIRT1 appears to correlate with osteophyte and PIIANP/CTX-II reduction at baseline, to potentially indicate baseline OA severity.