Protein biomarkers associated with pain mechanisms in osteoarthritis

Thudium, Christian S.; Löfvall, Henrik; Karsdal, Morten A.; Bay‐Jensen, Anne‐Christine; Bihlet, A.R.

doi:10.1016/j.jprot.2018.04.030

Cited by 29 publications

(32 citation statements)

References 146 publications

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“…Osteoarthritis (OA) is the most frequent form of arthritic disease around the world, resulting in destruction of joint tissues and debilitating pain. 1 The main risk factors for OA development are manifold with the local and systemic reasons, including genetics, obesity, age, gender, previous joint trauma, as well as other underlying diseases. 2 This disease is related to numerous comorbidities, which considerably lowers the quality of life for OA patients.…”

Section: Introductionmentioning

confidence: 99%

Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

Dong¹,

Li²,

Fang³

et al. 2021

JPR

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Exosome-encapsulated microRNAs (miRNAs) are being considered as either diagnostic or predictive markers in different types of diseases. Here, we discussed the effects of exosome-encapsulated miR-127-3p from bone marrow-derived mesenchymal stem cells (BM-MSCs) on osteoarthritis (OA). Methods: BM-MSCs and primary chondrocytes were isolated from Sprague Dawley rats. IL-1β was utilized to treat chondrocytes to mimic an OA in vitro model, and exosomes extracted from BM-MSCs were utilized to treat chondrocytes so as to verify their protective effects on OA. Through online website prediction and experiments confirmation, we found the most significantly enriched miRNA in exosomes and elucidated the effect of this miRNA on the therapeutic effect of exosomes by interfering with its expression. Also, the genes targeted by the miRNA and the involved pathway were also found through bioinformatics analysis and experimental research, thereby probing into the protective mechanism of exosomes on chondrocytes. Results: Exosomes derived from BM-MSCs restricted the IL-1β-induced chondrocytes damage. miR-127-3p was found to be enriched in exosomes, and the protective effect of exosomes was reversed by miR-127-3p inhibition. miR-127-3p targeted CDH11, and overexpressed CDH11 in chondrocytes weakened the therapeutic effect of exosomes. IL-1β treatment resulted in the activation of the Wnt/β-catenin pathway in chondrocytes. Exosomes treatment could inhibit the activation of this pathway, and overexpressed CDH11 reversed the inhibitory effect of exosomes on this pathway. Conclusion: This study suggests that exosomal miR-127-3p derived from BM-MSCs inhibits CDH11 in chondrocytes, thereby blocking the Wnt/β-catenin pathway activation and relieving chondrocyte damage in OA.

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Section: Introductionmentioning

confidence: 99%

Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

Dong¹,

Li²,

Fang³

et al. 2021

JPR

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“…The absence of objective diagnostic tools is leading scientists to the identification of chronic pain markers, in order to improve the diagnostic process and reduce the risks of diagnostic delays and misdiagnosis [53,54]. An objective diagnosis could allow a better classification of these chronic diseases, by clarifying pathogenetic mechanism, prognosis and/or response to treatment, opening the way to personalized medicine.…”

Section: Discussionmentioning

confidence: 99%

“…An objective diagnosis could allow a better classification of these chronic diseases, by clarifying pathogenetic mechanism, prognosis and/or response to treatment, opening the way to personalized medicine. The importance of biomarkers to guide chronic pain diagnosis and treatment properly assumes an even greater impact, considering the lack of valid molecular markers for diagnosis for all the chronic pain states [53,55].…”

Section: Discussionmentioning

confidence: 99%

Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases

Raffaeli

Malafoglia

Bonci

et al. 2020

IJMS

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Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane. Here we analyzed the role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM and osteoarthritis (OA) patients. We enrolled three groups of females: FM patients, OA patients (chronic pain control group) and healthy subjects (pain-free negative control group). We collected blood samples to apply immunophenotyping analysis. Written tests were administrated for psychological analysis. Data were statistically analyzed. Final results showed that the percentage of Mu-positive B cells were statistically lower in FM and OA patients than in pain-free subjects. A low expression of Mu-positive B cell was not associated with the psychological characteristics investigated. In conclusion, here we propose the percentage of Mu-positive B cells as a biological marker for an objective diagnosis of chronic pain suffering patients, also contributing to the legitimacy of FM as a truly painful disease.

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“…CTX-II (C-terminal peptide of type II collagen) belongs to the marker of tissue degradation and is the most widely studied and promising molecular biomarker of all BIPED categories [10]. In the study of steady-state destruction of cartilage, its degradation product C2C is also a highly sensitive targeted molecular biomarker [11]. CTX-II is highly correlated with the occurrence, development, injury degree, bone marrow lesion and osteophyte formation of OA [12,13].…”

Section: Introductionmentioning

confidence: 99%

Potential value of combining CTX-II with C2C in evaluating and diagnosing early rat osteoarthritis

Shen¹,

Zhang²,

Ma³

et al. 2020

Preprint

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Background This article aims to study the changes of CTX-II and C2C biomarker concentrations during the pathogenesis of osteoarthritis with SD rats as the research object. Through the longitudinal and joint detection of the content of CTX-II and C2C markers in the serum of anterior cruciate ligament resection (ACLT) rats, the evaluation and early diagnosis of OA disease can be realized, and the theoretical basis for the rapid diagnosis technology of OA can be provided. Methods SD rats were randomly divided into two groups: Sham operation group and OA model group. The OA model was established by anterior cruciate ligament excision (ACLT) for 2, 4, 6, 8, and 10 weeks, respectively. The cartilage gross score and Mankin score were used to evaluate the model. The tibia of the right hind limb was sampled for pathological histology and HE staining. The collected blood samples are used to detect changes in the concentration of CTX-II and C2C in serum. The receiver operating characteristic curve (ROC) was used to compare the area under the curve (AUC) of CTX-II, C2C and combined biomarkers. Results In the model group, the content of CTX-II and C2C in SD rat serum increased significantly, and the content of CTX-II and C2C increased with the prolonged modeling time, which was time dependent; The levels of CTX-II and C2C in the serum of rats in the sham operation group did not change significantly; both macroscopic observations and Mankin scores increased significantly. The AUC of the combined biomarker is higher than that of CTX-II and C2C. Finally, CTX-II and C2C levels were positively correlated with Mankin score. Conclusion Early combined detection of serum CTX-II and C2C concentrations has potential value for the evaluation and diagnosis of osteoarthritis.

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Protein biomarkers associated with pain mechanisms in osteoarthritis

Cited by 29 publications

References 146 publications

Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

Exosome-Encapsulated microRNA-127-3p Released from Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Osteoarthritis Through Regulating CDH11-Mediated Wnt/β-Catenin Pathway

Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases

Potential value of combining CTX-II with C2C in evaluating and diagnosing early rat osteoarthritis

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