Lysophosphatidylcholines to phosphatidylcholines ratio predicts advanced knee osteoarthritis

Zhang, Weidong; Sun, Guang; Aitken, Dawn; Likhodii, Sergei; Liu, Ming; Martin, Glynn; Furey, Andrew; Randell, Edward; Rahman, Proton; Jones, Graeme; Zhai, Guangju

doi:10.1093/rheumatology/kew207

Cited by 70 publications

(76 citation statements)

References 50 publications

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“…These results are in agreement with previous reports in which 16 O exhibited a higher degree of change in lipids compared to 1 H [28,29]. An increase in overall plasma PC levels with a concomitant rise in LysoPCs levels is suggestive of oxidative stress and inflammation upon exposure to 16 O [30]. Alterations in metabolome following exposure to low dose high-LET radiation have previously been reported by our group [31].…”

Section: Discussionsupporting

confidence: 93%

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

et al. 2020

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Long-term exposures to low dose space radiation may have adverse effects on human health during missions in deep space. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as biomarkers of organ- and tissue-specific radiation injury, particularly of injuries that appear weeks or months after radiation exposure. To assess the feasibility of using plasma metabolic and lipidomic profiles as biomarkers of injury from space radiation, we used a mouse model of exposure to low doses of oxygen ions (16O) and protons (1H). Plasma profiles were compared with those of mice exposed to γ-rays as a reference set. Our results demonstrate major changes in glycerophospholipid metabolism, amino acid metabolism, as well as fatty acid metabolism. We also observed dyslipidemia and lipid peroxidation, suggesting an inflammatory phenotype with possible long-term consequences to overall health upon exposure to low doses of high linear energy transfer (LET) radiation.

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Section: Discussionsupporting

confidence: 93%

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

et al. 2020

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“…Plasmatic lysophosphatidylcholine to phosphatidylcholine ratio was identified as a potential new OA biomarker for predicting advanced knee OA. Besides, it was confirmed that BCAAs to histidine ratio was associated with knee OA ( 47 ).…”

Section: Introductionmentioning

confidence: 90%

Metabolomics as a promising tool for early osteoarthritis diagnosis

Sousa

Santos

Duarte

et al. 2017

Braz J Med Biol Res

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Osteoarthritis (OA) is the main cause of disability worldwide, due to progressive articular cartilage loss and degeneration. According to recent research, OA is more than just a degenerative disease due to some metabolic components associated to its pathogenesis. However, no biomarker has been identified to detect this disease at early stages or to track its development. Metabolomics is an emerging field and has the potential to detect many metabolites in a single spectrum using high resolution nuclear magnetic resonance (NMR) techniques or mass spectrometry (MS). NMR is a reproducible and reliable non-destructive analytical method. On the other hand, MS has a lower detection limit and is more destructive, but it is more sensitive. NMR and MS are useful for biological fluids, such as urine, blood plasma, serum, or synovial fluid, and have been used for metabolic profiling in dogs, mice, sheep, and humans. Thus, many metabolites have been listed as possibly associated to OA pathogenesis. The goal of this review is to provide an overview of the studies in animal models and humans, regarding the use of metabolomics as a tool for early osteoarthritis diagnosis. The concept of osteoarthritis as a metabolic disease and the importance of detecting a biomarker for its early diagnosis are highlighted. Then, some studies in plasma and synovial tissues are shown, and finally the application of metabolomics in the evaluation of synovial fluid is described.

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“…Furthermore, none of the measured lipids correlated with OA severity within the hCRP-tg group. Lysophosphatidylcholines (LPC) to phosphatidylcholines (PC) ratio, as a general indicator of inflammatory status and possible predictor of advanced knee OA in humans 24 , dropped shortly after HFD switch (hCRP-tg: from 0.83 [0.62e1.10] to 0.70 [0.38e0.80]; wild- Fig. 2(A).…”

Section: Lipid Metabolism Comparable Between Genotypesmentioning

confidence: 99%

Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet

Kozijn

Tartjiono

Ravipati

et al. 2019

Osteoarthritis and Cartilage

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Objective: C-reactive protein (CRP) levels can be elevated in osteoarthritis (OA) patients. In addition to indicating systemic inflammation, it is suggested that CRP itself can play a role in OA development. Obesity and metabolic syndrome are important risk factors for OA and also induce elevated CRP levels. Here we evaluated in a human CRP (hCRP)-transgenic mouse model whether CRP itself contributes to the development of 'metabolic' OA. Design: Metabolic OA was induced by feeding 12-week-old hCRP-transgenic males (hCRP-tg, n ¼ 30) and wild-type littermates (n ¼ 15) a 45 kcal% high-fat diet (HFD) for 38 weeks. Cartilage degradation, osteophytes and synovitis were graded on Safranin O-stained histological knee joint sections. Inflammatory status was assessed by plasma lipid profiling, flow cytometric analyses of blood immune cell populations and immunohistochemical staining of synovial macrophage subsets. Results: Male hCRP-tg mice showed aggravated OA severity and increased osteophytosis compared with their wild-type littermates. Both classical and non-classical monocytes showed increased expression of CCR2 and CD86 in hCRP-tg males. HFD-induced effects were evident for nearly all lipids measured and indicated a similar low-grade systemic inflammation for both genotypes. Synovitis scores and synovial macrophage subsets were similar in the two groups. Conclusions: Human CRP expression in a background of HFD-induced metabolic dysfunction resulted in the aggravation of OA through increased cartilage degeneration and osteophytosis. Increased recruitment of classical and non-classical monocytes might be a mechanism of action through which CRP is involved in aggravating this process. These findings suggest interventions selectively directed against CRP activity could ameliorate metabolic OA development.

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Lysophosphatidylcholines to phosphatidylcholines ratio predicts advanced knee osteoarthritis

Abstract: We identified the ratio of lysoPCs to PCs as a novel metabolic marker for predicting advanced knee OA. Further studies are required to examine whether this ratio can predict early OA change.

Cited by 70 publications

References 50 publications

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model

Metabolomics as a promising tool for early osteoarthritis diagnosis

Human C-reactive protein aggravates osteoarthritis development in mice on a high-fat diet

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