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

Miya Marco, Mylène Jansen, Goran van der Weiden, Eli Reich, Yonathan H. Maatuf, Simon C. Mastbergen, Mona Dvir-Ginzberg

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

Original languageAmerican English
Article number106
JournalArthritis Research and Therapy
Volume26
Issue number1
DOIs
StatePublished - Dec 2024

Keywords

  • ELISA
  • Endotype
  • Full-length Sirt1
  • Joint distraction
  • Osteoarthritis
  • Serum biomarker

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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