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Biomarkers in Osteoarthritis

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 20513

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Prof. Dr. Sten Rasmussen

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Department of Clinical Medicine, Aalborg University, 9220 Aalborg, Denmark
Interests: biomarkers; knee; osteoarthritis; sports medicine; arthroscopy
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

There is an increasing incidence and prevalence of osteoarthritis due to the increasing population, increasing age, increasing BMI, and increasing multi-morbidity. Pain without cause for more than three months and degenerative changes on MRI indicate early osteoarthritis before degenerative changes are obvious on X-ray. Based on this accurate diagnosis and risk–benefit stratification it is essential to decide when to treat and to avoid overload on health costs.

Biomarkers are different indicators of physiological changes or disease processes and include physical, functional, and biochemical indicators. They provide information in determining or predicting disease prognosis, response to therapy, adverse events, interactions, and risks. There are a huge number of biomarkers in use, making it difficult to decide which biomarkers to use in osteoarthritis. Further, it may be a challenge to evaluate the reliability, validity, and responsiveness of a biomarker.

This calls for better, precise, and easy biomarkers to decide the optimal treatment at the right time, to follow-up on treatment, and to perform a useful follow-up.

This Special Issue aims to gather a collection of cutting-edge research within the different types of biomarkers to improve decision-making. The aim is to publish original discoveries within osteoarthritis form all medical and biomedical disciplines. The scope is to provide what is new and what is the trend in biomarkers in relation to osteoarthritis.

We welcome submissions on, but not limited to, the following topics within osteoarthritis:

Biochemical;

Proteomics;

Molecular biology;

Scoring;

Functional;

Diagnostic;

Prognostic;

Predictor;

Outcome;

Patient-reported outcome;

Pathophysiology.

Prof. Dr. Sten Rasmussen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

osteoarthritis
biomarker
biochemical
proteomic
molecular biology
scoring
functional
diagnostic
prognostic
predictor
outcome
patient-reported outcome
pathophysiology

Related Special Issue

Biomarkers in Osteoarthritis-Volume 2 in Diagnostics (1 article)

Published Papers (9 papers)

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Research

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15 pages, 1412 KiB

Open AccessArticle

Risk Assessment of the Progression of Early Knee Osteoarthritis by Collagen Neoepitope C2C: A Longitudinal Study of an Estonian Middle-Aged Cohort

by Liisa Kuhi, Ann E. Tamm, Agu O. Tamm and Kalle Kisand

Diagnostics 2021, 11(7), 1236; https://doi.org/10.3390/diagnostics11071236 - 10 Jul 2021

Cited by 8 | Viewed by 1871

Abstract

One of the unmet needs to be addressed is prognostic biomarkers for early knee osteoarthritis (kOA). We aimed to study the association of urinary collagen type-II C-terminal cleavage neoepitope (uC2C) with the emergence and progression of kOA. The longitudinal data of 330 subjects (aged 32–60 years) from an Estonian population-based cohort were used. The radiographic progression was evaluated by the grading system of Nagaosa et al. of knee compartments at baseline and three years later. The emerging kOA consisted of subjects with developing osteophytes or joint space narrowing, whereas kOA progressors showed aggravation of radiographic grade. Baseline uC2C levels were measured by the IBEX-uC2C assay. At baseline, the subjects were middle-aged (mean age, 47.6 years) and overweight (mean BMI, 28.0 kg/m²), and the majority of them (51.2%) had a diagnosis of kOA grade 1. Multiple logistic regression models adjusted for sex, age, and BMI were used for risk calculations. We demonstrate that increased uC2C accurately predicted the risk of emerging of kOA (OR = 5.87 (1.71–20.22); AUC = 0.79) compared with controls without radiographic kOA over 12 years. However, the most accurate prediction of progression by the biomarker was found in women (OR = 23.0 (2.2–245), AUC = 0.91). In conclusion, uC2C may be a promising candidate as a prognostic biomarker for kOA progression, particularly of emerging kOA in women. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

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11 pages, 270 KiB

Open AccessArticle

Association between miRNA Target Sites and Incidence of Primary Osteoarthritis in Women from Volga-Ural Region of Russia: A Case-Control Study

by Anton Tyurin, Daria Shapovalova, Halida Gantseva, Valentin Pavlov and Rita Khusainova

Diagnostics 2021, 11(7), 1222; https://doi.org/10.3390/diagnostics11071222 - 6 Jul 2021

Cited by 4 | Viewed by 2012

Abstract

Over the past decades, numerous studies on the genetic markers of osteoarthritis (OA) have been conducted. MiRNA targets sites are a promising new area of research. In this study, we analyzed the polymorphic variants in 3′ UTR regions of COL1A1, COL11A1, ADAMTS5, MMP1, MMP13, SOX9, GDF5, FGF2, FGFR1, and FGFRL1 genes to examine the association between miRNA target site alteration and the incidence of OA in women from the Volga-Ural region of Russia using competitive allele-specific PCR. The T allele of the rs9659030 was associated with generalized OA (OR = 2.0), whereas the C allele of the rs229069 was associated with total OA (OR = 1.43). The T allele of the rs13317 was associated with the total OA (OR = 1.67). After Benjamini-Hochberg correction, only rs13317 remained statistically significant. According to ethnic heterogeneity, associations between the T allele (rs1061237) with OA in women of Russian descent (OR = 1.77), the G allele (rs6854081) in women of Tatar descent (OR = 4.78), the C allele (rs229069) and the T allele (rs73611720) in women of mixed descent and other ethnic groups (OR = 2.25 and OR = 3.02, respectively) were identified. All associations remained statistically significant after Benjamini-Hochberg correction. Together, this study identified miRNA target sites as a genetic marker for the development of OA in various ethnic groups. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

14 pages, 1125 KiB

Open AccessArticle

Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers

by Yoon Hae Kwak, Dae-Kyung Kwak, Hyun-Soo Moon, Nan Young Kim, Jae-Sung Yee and Je-Hyun Yoo

Diagnostics 2021, 11(2), 258; https://doi.org/10.3390/diagnostics11020258 - 7 Feb 2021

Cited by 5 | Viewed by 1702

Abstract

High tibial osteotomy (HTO) is an effective alternative for medial compartmental knee osteoarthritis (OA). Circulating microRNAs (miRNAs) are known to serve as OA-related biomarkers. The present study investigated the differential expression of serum miRNAs before and after HTO to identify potential miRNAs as prognostic biomarkers. miRNA-polymerase chain reaction (PCR) arrays were used to screen for miRNAs in the serum at preoperative and 6-month postoperative time points from six patients, and the differentially expressed miRNAs identified in the profiling stage were validated using real-time PCR at post-operative months 6 and 18 in 27 other HTO-treated patients. Among 84 miRNAs involved in the inflammatory process, three (miR-19b-3p, miR-29c-3p, and miR-424-5p) showed differential expression patterns in the profiling stage (p = 0.011, 0.015, and 0.021, respectively). Levels of these three and four other miRNAs (miR-140-3p, miR-454-3p, miR-let-7e-5p, and miR-885-5p) known to be related to OA progression were evaluated in the serum of 27 patients. Only four miRNAs (miR-19b-3p, miR-140-3p, miR-454-3p, and miR-let-7e-5p) were significantly upregulated at postoperative month 6 (p = 0.003, 0.005, 0.004, and 0.004, respectively), and only miR-140-3p was significantly upregulated up to 18 months after operation (p = 0.003). Together, this study reveals the significantly upregulated serum miRNAs after HTO as potential prognostic biomarkers; however, further studies are warranted to elucidate their clinical implications. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

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12 pages, 848 KiB

Open AccessArticle

Serum Biomarkers of Inflammation and Turnover of Joint Cartilage Can Help Differentiate Psoriatic Arthritis (PsA) Patients from Osteoarthritis (OA) Patients

by Michał Waszczykowski, Anna Fabiś-Strobin, Igor Bednarski, Aleksandra Lesiak, Joanna Narbutt and Jarosław Fabiś

Diagnostics 2021, 11(1), 52; https://doi.org/10.3390/diagnostics11010052 - 31 Dec 2020

Cited by 8 | Viewed by 2239

Abstract

The aim of this study was to find characteristic biomarkers in the serum of patients with osteoarthritis (OA) and psoriatic arthritis (PsA) responsible for inflammation and destruction of joint cartilage, which could differentiate these two diseases. The study included 67 people: 22 patients with knee OA, 22 patients with PsA, and 23 individuals who were the control group of healthy individuals (HC). The concentration of IL-18, IL-20, IL-6, MMP-1, MMP-3, COMP, PG-AG, and YKL-40 in serum were determined. Among the OA and PsA patients group, the radiological assessment and clinical assessment were also performed. The concentration of 7 out of 8 of examined biomarkers (except MMP-1) was statistically significantly higher in the serum of patients with OA and PsA than in the control group. Compering OA and PsA groups only, the serum PG-AG level in OA patients was statistically significantly higher than in PsA patients (p < 0.001). The results of univariate and multivariate logistic regression analysis comparing OA and PsA biomarker serum levels identified PG-AG and COMP as markers that are significantly different between patients with OA and PsA (odds ratio 0.995 and 1.003, respectively). The ROC curve constructed using the model with age showed PG-AG and COMP had an AUC of 0.907. The results of this study show that COMP and PG-AG may be sensitive markers differentiating patients with osteoarthiritis from psoriatic arthritis. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

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17 pages, 13184 KiB

Open AccessArticle

High-Density Mineralized Protrusions and Central Osteophytes: Associated Osteochondral Junction Abnormalities in Osteoarthritis

by Alecio F. Lombardi, Qingbo Tang, Jonathan H. Wong, Judith L. Williams, Saeed Jerban, Yajun Ma, Hyungseok Jang, Jiang Du and Eric Y. Chang

Diagnostics 2020, 10(12), 1051; https://doi.org/10.3390/diagnostics10121051 - 5 Dec 2020

Cited by 4 | Viewed by 1747

Abstract

The aim of this study was to determine the association between high-density mineralized protrusions (HDMPs) and central osteophytes (COs), and describe the varying appearance of these lesions using advanced clinical imaging and a novel histological protocol. Seventeen consecutive patients with clinically advanced knee osteoarthritis undergoing knee arthroplasty were included. Surgical tissues containing the osteochondral region were investigated using computed tomography (CT); a subset was evaluated using confocal microscopy with fluorescence. Tissues from seven subjects (41.2%) contained HDMPs, and tissues from seven subjects (41.2%) contained COs. A significant association between HDMPs and COs was present (p = 0.003), with 6 subjects (35.2%) demonstrating both lesions. In total, 30 HDMPs were found, most commonly at the posterior medial femoral condyle (13/30, 43%), and 19 COs were found, most commonly at the trochlea (5/19, 26.3%). The HDMPs had high vascularity at their bases in cartilaginous areas (14/20, 70%), while the surrounding areas had elevated levels of long vascular channels penetrating beyond the zone of calcified cartilage (p = 0.012) compared to HDMP-free areas. Both COs and HDMPs had noticeable bone-resorbing osteoclasts amassing at the osteochondral junction and in vascular channels entering cartilage. In conclusion, HDMPs and COs are associated lesions in patients with advanced knee osteoarthritis, sharing similar histologic features, including increased vascularization and metabolic bone activity at the osteochondral junction. Future studies are needed to determine the relationship of these lesions with osteoarthritis progression and symptomatology. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

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10 pages, 1219 KiB

Open AccessArticle

Positive Association of Serum Alkaline Phosphatase Level with Severe Knee Osteoarthritis: A Nationwide Population-Based Study

by Hye-Min Park, Jun-Hyuk Lee and Yong-Jae Lee

Diagnostics 2020, 10(12), 1016; https://doi.org/10.3390/diagnostics10121016 - 27 Nov 2020

Cited by 12 | Viewed by 2834

Abstract

Serum alkaline phosphatase (ALP), a well-known marker of hepatobiliary and bone disorders, has recently been discovered to be a biochemical marker of cardiometabolic diseases and chronic low-grade inflammation. We aimed to evaluate the association of serum ALP level with knee osteoarthritis in the general population. The study included 3060 men and women aged ≥50 years who participated in the 2009–2011 Korea National Health and Nutrition Examination Survey. The participants were categorized into three groups based on log-transformed serum ALP level as follows: T1 (1.74–2.32), T2 (2.33–2.43), and T3 (2.44–3.01). Their radiographs were evaluated by two well-trained radiologists using the Kellgren–Lawrence (KL) grading system. After excluding those with KL Grade 0, we categorized the remaining participants into two groups, a severe osteoarthritis group (KL Grade 4) and a non-severe osteoarthritis group (KL Grades 1 to 3). The odds ratios (ORs) with 95% confidence intervals (CIs) of severe osteoarthritis according to the tertiles of log-transformed serum ALP levels of patients with osteoarthritis were calculated using a weighted multivariate logistic regression analysis. Compared with T1, the adjusted ORs (95% CIs) for severe osteoarthritis of the T3 serum ALP group was 1.613 (1.087–2.394; p = 0.018) after adjusting for the confounding variables. Conclusively, serum ALP activity was independently and positively associated with severe knee osteoarthritis in middle-aged and older adults. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

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16 pages, 268 KiB

Open AccessArticle

Circulating Levels of Visceral Adipose Tissue-Derived Serine Protease Inhibitor (Vaspin) Appear as a Marker of Musculoskeletal Pain Disability

by Nader Tarabeih, Alexander Kalinkovich, Adel Shalata and Gregory Livshits

Diagnostics 2020, 10(10), 797; https://doi.org/10.3390/diagnostics10100797 - 8 Oct 2020

Cited by 13 | Viewed by 2254

Abstract

Musculoskeletal pain (MSP), specifically low back pain (LBP), is often associated with several adipose tissue-derived cytokines (adipokines) and body composition, but their correlations with the LBP-related disability/severity phenotypes remain poorly understood. In this cross-sectional study, two self-reported validated questionnaires were used to collect back pain and disability data in an ethnically homogeneous family-based population sample (N = 1078). Plasma levels of relatively new adipokines, vaspin and adipsin, were detected by ELISA. Body composition parameters, including fat, skeletal muscle mass, extracellular water (ECW), and others were assessed through bioelectrical impedance analysis (BIA) technology. Statistical analysis was conducted, accounting for the familial composition of the sample. The multiple regression analyses with four LBP-related phenotypes as dependent variables consistently showed, for the first time, the significant associations with vaspin levels, regardless of other covariates. The odds ratios (OR)/SD ranged between 1.24 (95%CI = 1.03–1.50) and 1.33 (95%CI = 1.07–1.64), depending on the LBP phenotype. Among the tested body composition covariates, only ECW levels displayed consistent and highly significant associations with all tested LBP phenotypes (OR from 1.43, 95%CI = 1.14–1.79 to 1.68, 95%CI = 1.26–2.24). The results clearly suggest that circulating concentrations of vaspin and ECW levels could serve as biomarkers of MSP/LBP severity and complications. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

Review

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18 pages, 383 KiB

Open AccessReview

Common Biochemical and Magnetic Resonance Imaging Biomarkers of Early Knee Osteoarthritis and of Exercise/Training in Athletes: A Narrative Review

by Johanne Martel-Pelletier, Ginette Tardif, Patrice Paiement and Jean-Pierre Pelletier

Diagnostics 2021, 11(8), 1488; https://doi.org/10.3390/diagnostics11081488 - 17 Aug 2021

Cited by 5 | Viewed by 2785

Abstract

Knee osteoarthritis (OA) is the most common joint disease of the world population. Although considered a disease of old age, OA also affects young individuals and, more specifically among them, those practicing knee-joint-loading sports. Predicting OA at an early stage is crucial but remains a challenge. Biomarkers that can predict early OA development will help in the design of specific therapeutic strategies for individuals and, for athletes, to avoid adverse outcomes due to exercising/training regimens. This review summarizes and compares the current knowledge of fluid and magnetic resonance imaging (MRI) biomarkers common to early knee OA and exercise/training in athletes. A variety of fluid biochemical markers have been proposed to detect knee OA at an early stage; however, few have shown similar behavior between the two studied groups. Moreover, in endurance athletes, they are often contingent on the sport involved. MRI has also demonstrated its ability for early detection of joint structural alterations in both groups. It is currently suggested that for optimal forecasting of early knee structural alterations, both fluid and MRI biomarkers should be analyzed as a panel and/or combined, rather than individually. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

13 pages, 617 KiB

Open AccessReview

Data Integration Reveals the Potential Biomarkers of Circulating MicroRNAs in Osteoarthritis

by Thuan Duc Lao and Thuy Ai Huyen Le

Diagnostics 2021, 11(3), 412; https://doi.org/10.3390/diagnostics11030412 - 28 Feb 2021

Cited by 8 | Viewed by 2042

Abstract

The abnormal expression of circulating miRNAs (c-miRNAs) has become an emerging field in the development of miRNAs-based diagnostic and therapeutic tools for human diseases, including osteoarthritis (OA). OA is the most common form of arthritis leading to disability and a major socioeconomic burden. The abnormal expression of miRNAs plays important roles in the pathogenesis of OA. Unraveling the role of miRNAs in the pathogenesis of OA will throw light on the potential for the development of miRNAs-based diagnostic and therapeutic tools for OA. This article reviews and highlights recent advances in the study of miRNAs in OA, with specific demonstration of the functions of miRNA, especially c-miRNA, in OA pathogenesis as well as its potential implication in the treatment of OA. Based on a systematic literature search using online databases, we figured out the following main points: (1) the integrative systematic review of c-mRNAs and its target genes related to OA pathogenesis; (2) the potential use of c-miRNAs for OA diagnosis purposes as potential biomarkers; and (3) for therapeutic purposes, and we also highlight certain remedies that regulate microRNA expression based on its target genes. Full article

(This article belongs to the Special Issue Biomarkers in Osteoarthritis)

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