Synovial tissue metabolomic profiling reveal biomarkers of synovial inflammation in patients with osteoarthritis
Murillo-Saich, Jessica D. (University of California. Department of Medicine)
Coras, Roxana (Universitat Autònoma de Barcelona. Departament de Medicina)
Meyer, Robert (San Diego VA Healthcare Service)
Llorente, Cristina (University of California. Department of Medicine)
Lane, Nancy E. (University of California. Department of Medicine)
Guma, Monica 1971- (San Diego VA Healthcare Service)

Fecha:	2022
Resumen:	Inflammatory responses are associated with changes in tissue metabolism. Prior studies find altered metabolomic profiles in both the synovial fluid (SF) and serum of osteoarthritis subjects. Our study determined the metabolomic profile of synovial tissue (ST) and SF of individuals with osteoarthritis (OA) and its association with synovial inflammation. 37 OA ST samples were collected during joint replacement, 21 also had SF. ST samples were fixed in formalin for histological analysis, cultured (explants) for cytokine analysis by enzyme-linked immunosorbent assay, or snap-frozen for metabolomic analysis. ST samples were categorized by Krenn synovitis score and picrosirius red. CD68 and vimentin expression was assessed by immunohistochemistry and semi-quantified using Image J. Proton-nuclear magnetic resonance (1 H NMR) was used to acquire a spectrum from ST and SF samples. Chenomx NMR suite 8. 5 was used for metabolite identification and quantification. Metaboanalyst 5. 0, SPSS v26, and R (v4. 1. 2) were used for statistical analysis. 42 and 29 metabolites were detected in the ST and SF respectively by 1 H NMR. Only 3 metabolites, lactate, dimethylamine, and creatine positively correlated between SF and ST. ST concentrations of several metabolites (lactate, alanine, fumarate, glutamine, glycine, leucine, lysine, methionine, trimethylamine N -oxide, tryptophan and valine) were associated with synovitis score, mostly to the lining score. IL-6, acetoacetate, and tyrosine in SF predicted high Krenn synovitis scores in ST. Metabolomic profiling of ST identified metabolic changes associated with inflammation. Further studies are needed to determine whether metabolomic profiling of synovial tissue can identify new therapeutic targets in osteoarthritis.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Inflammation ; Fibrosis ; Metabolomic ; Synovial fluid
Publicado en:	Osteoarthritis and Cartilage Open, Vol. 4 (july 2022) , ISSN 2665-9131

DOI: 10.1016/j.ocarto.2022.100295
PMID: 36474936

10 p, 2.3 MB

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