Metabolomics with severity of radiographic knee osteoarthritis and early phase synovitis in middle-aged women from the Iwaki Health Promotion Project: a cross-sectional study

Abstract

Background Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study. Methods We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed. Results Among the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine (p = 0.009), uric acid (p = 0.024), and tyrosine (p = 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA (p < 0.001, area under the curve 0.714, odds ratio 3.7). Conclusion Large sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis.

Radiographic OA, bone marrow lesions, higher body mass index and medial meniscal root tears are significantly associated with medial meniscus extrusion with OA or medial meniscal tears: a systematic review and meta-analysis

“…The severity of knee OA was graded from 0 to 4 using the Kellgren‐Lawrence (KL) score based on joint space narrowing and osteophyte formation. Radiographic OA was defined as the knee with KL grade ≥ 2 [40]. The previous study has established a significant correlation between MME and radiographic OA [3].…”

Multiset partial least squares with rank order of groups for integrating multi-omics data

“…This becomes more important when we select significant compounds by using multiset PLS-ROG loading. In our previous study of PLS-ROG [10, 16], we could identify significant metabolites with rank order of groups by using PLS-ROG loading, if only the response variable showed rank order of the groups. On the other hands, we could identify compounds with rank order of groups by using multiset PLS-ROG loading only when both the explanatory and response variables showed rank order of groups.…”

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts

“…Given the chondrodegenerative nature of OA, circulating molecules reflective of cartilage turnover represent extremely promising diagnostic and prognostic indicators. Notably, epitopes of Fibulin-3 (Fib3-1, Fib3-2, and Fib3-3), aggrecanase-generated aggrecan (ARGS), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type II collagen (CTX-II), along with metabolites like acylcarnitines, uric acids, cystine, and tyrosine, frequently exhibit altered levels in this condition [49][50][51][52][53][54][55].…”