Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post‐traumatic osteoarthritis

Abstract

ACL rupture is a major risk factor for post-traumatic osteoarthritis (PTOA) development. Little information exists on acute systemic metabolic indicators of disease development. Thirty-six female Lewis rats were randomized to Control or noninvasive anterior cruciate ligament rupture (ACLR) and to three post-injury time points: 72 h, 4 weeks, 10 weeks (n = 6). Serum was collected and analyzed by H nuclear magnetic resonance (NMR) spectroscopy and combined direct injection and liquid chromatography (LC)-mass spectrometry (MS)/MS (DI-MS). Univariate and multivariate statistics were used to analyze metabolomic data, and predictive biomarker models were analyzed by receiver operating characteristic (ROC) analysis. Topological pathway analysis was used to identify perturbed pathways. Two hundred twenty-two metabolites were identified by H NMR and DI-MS. Differences in the serum metabolome between ACLR and Control were dominated by medium- and long-chain acylcarnitine species. Further, decreases in several tryptophan metabolites were either found to be significantly different in univariate analysis or to play important contributory roles to multivariate model separation. In addition to acylcarnitines and tryptophan metabolites, glycine, carnosine, and D-mannose were found to differentiate ACLR from Control. Glycine, 9-hexadecenoylcarnitine, trans-2-Dodecenoylcarnitine, linoelaidyl carnitine, hydroxypropionylcarnitine, and D-Mannose were identified as biomarkers with high area under ROC curve values and high predictive accuracies. Our analysis provides new information regarding the potential contribution of inflammatory processes and immune dysregulation to the onset and progression of PTOA following ACL injury. As these processes have most commonly been associated with inflammatory arthropathies, larger-scale studies elucidating their involvement in PTOA development and progression are necessary. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1969-1979, 2018.

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

“…CA has recently been investigated for its protective role, with interactions between human OA chondrocytes and 4-hydroxylnoneal (HNE) modified type II collagen affecting cell functions and phenotypes [ 76 ]. K. C. Baker and co-workers examined the metabolic serum profile after ACLT surgery, focusing on inflammatory and immune dysregulation related proteins in OA rats [ 77 ]. Chondrocytes and synoviocyte hyperplasia, as well as articular cartilage degradation, all contribute significantly to the development and progression of knee OA [ 78 ].…”

Integrated Analysis of the Alterations in Gut Microbiota and Metabolites of Mice Induced After Long-Term Intervention With Different Antibiotics

“…Since the decrease in SCFAs could increase intestinal permeability, the change could also have a comprehensive effect on immune response. In addition, tryptophan and its metabolites such as kynurenic acid, serotonin, and quinolinic acid can also exert anti-inflammatory effects and decreased severity of dextran sodium sulfate (DSS)-induced colitis in mice (Etienne-Mesmin et al, 2017 ; Maerz et al, 2018 ). The other metabolite, L-arginine, has proven to inhibit inflammatory response and oxidative stress induced by LPS (Qiu et al, 2019 ).…”

Metabolomic Profiling in the Characterization of Degenerative Bone and Joint Diseases

“…The second group was associated predominately with structural degradation-associated features, including alterations in the glycosaminoglycan (GAG) metabolism, tryptophan metabolism, and ascorbate degradation [18]. An altered GAG metabolism may reflect the direct catabolism of normally GAG-rich articular cartilage, while the tryptophan metabolism in the context of joint diseases has been associated with the inflammation and expansion of pro-inflammatory T-lymphocyte populations, including T h 17 cells [19]. In a series of 25 patients with OA, Zheng et al analyzed synovial fluid extracted in the setting of total knee arthroplasty (TKA) using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS), and showed six metabolites strongly associated with OA, including glutamine, 1,5-anhydroglucitol, gluconic lactone, tyramine, threonine, and 8-aminocaprylic acid [20].…”