Metabolomics as a promising tool for early osteoarthritis diagnosis

Sousa, Eduardo Branco de; Santos, Gilson Costa dos; Duarte, Maria Eugênia Leite; Moura‐Neto, Vivaldo; Aguiar, Diego Pinheiro

doi:10.1590/1414-431x20176485

Cited by 36 publications

(32 citation statements)

References 54 publications

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“…To achieve this goal, we performed a metabolomics analysis of the synovial fluid using NMR. Metabolomics involves the study of the metabolites present in a biological system [15], allowing to evaluate the organism response to environmental stimuli [56], and may be useful as a tool to find an early OA biomarker [24].…”

Section: Discussionmentioning

confidence: 99%

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Osteoarthritic Synovial Fluid Modulates Cell Phenotype and Metabolic BehaviorIn Vitro

Sousa

Santos

Aguiar

et al. 2019

Stem Cells International

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Synovial fluid holds a population of mesenchymal stem cells (MSC) that could be used for clinical treatment. Our goal was to characterize the inflammatory and metabolomic profile of the synovial fluid from osteoarthritic patients and to identify its modulatory effect on synovial fluid cells. Synovial fluid was collected from non-OA and OA patients, which was centrifuged to isolate cells. Cells were cultured for 21 days, characterized with specific markers for MSC, and exposed to a specific cocktail to induce chondrogenic, osteogenic, and adipogenic differentiation. Then, we performed a MTT assay exposing SF cells from non-OA and OA patients to a medium containing non-OA and OA synovial fluid. Synovial fluid from non-OA and OA patients was submitted to ELISA to evaluate BMP-2, BMP-4, IL-6, IL-10, TNF-α, and TGF-β1 concentrations and to a metabolomic evaluation using 1H-NMR. Synovial fluid cells presented spindle-shaped morphology in vitro. Samples from OA patients formed a higher number of colonies than the ones from non-OA patients. After 21 days, the colony-forming cells from OA patients differentiated into the three mesenchymal cell lineages, under the appropriated induction protocols. Synovial fluid cells increased its metabolic activity after being exposed to the OA synovial fluid. ELISA assay showed that OA synovial fluid samples presented higher concentration of IL-10 and TGF-β1 than the non-OA, while the NMR showed that OA synovial fluid presents higher concentrations of glucose and glycerol. In conclusion, SFC activity is modulated by OA synovial fluid, which presents higher concentration of IL-10, TGF-β, glycerol, and glucose.

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Section: Discussionmentioning

confidence: 99%

“…Metabolomics involves the analysis of metabolic products in biological fluids or tissue samples, which has recently been investigated as a method for OA research [22, 23] and as a promising tool for early OA diagnosis [24]. Hence, synovial fluid has been the focus of metabolomic studies in humans and animal models involving OA [25–27].…”

Section: Introductionmentioning

confidence: 99%

Osteoarthritic Synovial Fluid Modulates Cell Phenotype and Metabolic BehaviorIn Vitro

Sousa

Santos

Aguiar

et al. 2019

Stem Cells International

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“… 24 Thus, this methodology holds huge potential in the analysis of biofluids to characterize the global metabolic profiles of various pathologies. 25 Hugle et al previously carried out NMR spectroscopy using human SF, identifying that septic arthritis SF could be distinguished from nonseptic arthritis SF via principal component analysis (PCA), although they were unable to identify the specific metabolites responsible for this discrimination. 26 To date, only one peer-reviewed publication has used NMR to investigate the whole metabolic profile of equine SF by comparing normal and osteoarthritic SF.…”

Section: Introductionmentioning

confidence: 99%

Synovial Fluid Metabolites Differentiate between Septic and Nonseptic Joint Pathologies

et al. 2018

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Osteoarthritis (OA), osteochondrosis (OC), and synovial sepsis in horses cause loss of function and pain. Reliable biomarkers are required to achieve accurate and rapid diagnosis, with synovial fluid (SF) holding a unique source of biochemical information. Nuclear magnetic resonance (NMR) spectroscopy allows global metabolite analysis of a small volume of SF, with minimal sample preprocessing using a noninvasive and nondestructive method. Equine SF metabolic profiles from both nonseptic joints (OA and OC) and septic joints were analyzed using 1D 1H NMR spectroscopy. Univariate and multivariate statistical analyses were used to identify differential metabolite abundance between groups. Metabolites were annotated via 1H NMR using 1D NMR identification software Chenomx, with identities confirmed using 1D 1H and 2D 1H 13C NMR. Multivariate analysis identified separation between septic and nonseptic groups. Acetate, alanine, citrate, creatine phosphate, creatinine, glucose, glutamate, glutamine, glycine, phenylalanine, pyruvate, and valine were higher in the nonseptic group, while glycylproline was higher in sepsis. Multivariate separation was primarily driven by glucose; however, partial-least-squares discriminant analysis plots with glucose excluded demonstrated the remaining metabolites were still able to discriminate the groups. This study demonstrates that a panel of synovial metabolites can distinguish between septic and nonseptic equine SF, with glucose the principal discriminator.

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“…Biomarkers related to OA lesions are attractive . EGR1 is a transcription factor for growth and differentiation and serves as a regulator in several biological processes .…”

Section: Discussionmentioning

confidence: 99%

Molecular changes in peripheral blood involving osteoarthritic joint remodelling

Zhang

Liu

et al. 2019

J of Oral Rehabilitation

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Biomarkers of temporomandibular joint (TMJ) osteoarthritis (OA) remain unknown. The objective was to detect whether molecular biomarkers from peripheral blood leucocytes (PBLs) engage in TMJ OA lesions. Thirty‐four six‐week‐old Sprague Dawley rats were used. The top upregulated gene ontology categories and gene‐fold changes in PBLs were detected by a microarray analysis comparing rats that received 20‐week unilateral anterior crossbite (UAC) treatment with age‐matched controls (n = 4). Twenty weeks of UAC treatment had been reported to induce TMJ OA‐like lesions. The other twenty‐four rats were randomly placed in the UAC and control groups at 12‐ and 20‐week time points (n = 6). The mRNA expression levels of the selected biomarkers derived from the microarray analysis and their protein expression in the alveolar bone and TMJ were detected. The microarray analysis indicated that the three most highly involved genes in PBLs were Egr1, Ephx1 and Il10, which were confirmed by real‐time PCR detection. The increased protein expression levels of the three detected molecules were demonstrated in cartilage and subchondral bone (P < 0.05), and increased levels of EPHX1 were reported in discs (P < 0.05); however, increased levels were not present in the alveolar bone. Immunohistochemistry revealed the increased distribution of EGR1‐positive, EXPH1‐positive and IL10‐positive cells predominantly in the osteochondral interface, with EXPH1 also present in TMJ discs. In conclusion, the increased mRNA expression of Egr1, Ephx1 and Il10 in PBLs may serve as potential biomarkers for developed osteoarthritic lesions relating to osteochondral interface hardness changes induced by dental biomechanical stimulation.

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Metabolomics as a promising tool for early osteoarthritis diagnosis

Cited by 36 publications

References 54 publications

Osteoarthritic Synovial Fluid Modulates Cell Phenotype and Metabolic BehaviorIn Vitro

Osteoarthritic Synovial Fluid Modulates Cell Phenotype and Metabolic BehaviorIn Vitro

Synovial Fluid Metabolites Differentiate between Septic and Nonseptic Joint Pathologies

Molecular changes in peripheral blood involving osteoarthritic joint remodelling

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