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Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 19416

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Special Issue Editors

Dr. Jorge A. Roman-Blas

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Bone and Joint Research Unit, Department of Rheumatology, Fundacion Jimenez Diaz, UAM, Madrid, Spain
Interests: osteoarthritis; osteoporosis; inflammatory arthritis; articular cartilage; chondrocytes; subchondral bone; bone biology; joint biology
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Prof. Dr. Gabriel Herrero-Beaumont

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Hospital Universitario Fundacion Jimenez Diaz, Bone and Joint Research Unit, Madrid, Spain
Interests: osteoarthritis; osteoporosis; inflammatory arthritis
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Dr. Raquel Largo

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Guest Editor

Osteoarticular Pathology Laboratory, IIS Fundación Jiménez Díaz, 28040 Madrid, Spain
Interests: osteoarthritis; osteoporosis; inflammatory arthritis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

More than 500 million people worldwide (7% of the global population) are affected by Osteoarthritis (OA), the most common joint disorder. OA is a leading cause of chronic disability in older individuals, leading to a large socioeconomical burden. As aging, obesity and poor lifestyle increase in the world population, the burden of OA could be even bigger than expected.

OA is an evolving and progressive disease that alters all joint structures. The action of relevant etiopathogenic mechanisms modulated by extra-articular risk factors leads to different clinical manifestations that depend on the most damaged joint tissue at a given time. Molecular endotypes and clinical phenotypes were proposed in early OA. Years later, the OA process has reached advanced stages as a more uniform disease that significantly affects the quality of life.

The complexity of the etiopathogenesis and subsequent diverse clinical manifestations have impeded the development of well-designed therapeutic interventions in OA. Nevertheless, significant research effort has been devoted to improving our understanding of the natural history of OA and to the design of therapeutic strategies aimed at main pathophysiological mechanisms achieving relevant progress in the last few years.

In this sense, this Special Issue aims at presenting studies in basic, translational, clinical, and epidemiological research committed to further contributing to the advancement of the OA field.

Dr. Jorge A. Roman-Blas
Prof. Dr. Gabriel Herrero-Beaumont
Dr. Raquel Largo
Guest Editors

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Keywords

osteoarthritis
articular cartilage
chondrocyte
subchondral bone
synovial membrane
muscle
meniscus
animal models
clinical studies
epidemiology

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Published Papers (7 papers)

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Research

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11 pages, 586 KiB

Open AccessArticle

Association between Metformin Use and Risk of Total Knee Arthroplasty and Degree of Knee Pain in Knee Osteoarthritis Patients with Diabetes and/or Obesity: A Retrospective Study

by Shibo Chen, Guangfeng Ruan, Muhui Zeng, Tianyu Chen, Peihua Cao, Yan Zhang, Jia Li, Xiaoshuai Wang, Shengfa Li, Su’an Tang, Shilong Lu, Tianxiang Fan, Yang Li, Weiyu Han, Jianye Tan, Changhai Ding and Zhaohua Zhu

J. Clin. Med. 2022, 11(16), 4796; https://doi.org/10.3390/jcm11164796 - 17 Aug 2022

Cited by 9 | Viewed by 2791

Abstract

Objectives: We aimed to examine whether metformin (MET) use is associated with a reduced risk of total knee arthroplasty (TKA) and low severity of knee pain in patients with knee osteoarthritis (OA) and diabetes and/or obesity. Methods: Participants diagnosed with knee OA and diabetes and/or obesity from June 2000 to July 2019 were selected from the information system of a local hospital. Regular MET users were defined as those with recorded prescriptions of MET or self-reported regular MET use for at least 6 months. TKA information was extracted from patients’ surgical records. Knee pain was assessed using the numeric rating scale. Log-binomial regression, linear regression, and propensity score weighting (PSW) were performed for statistical analyses. Results: A total of 862 participants were included in the analyses. After excluding missing data, there were 346 MET non-users and 362 MET users. MET use was significantly associated with a reduced risk of TKA (prevalence ratio: 0.26, 95% CI: 0.15 to 0.45, p < 0.001), after adjustment for age, gender, body mass index, various analgesics, and insurance status. MET use was significantly associated with a reduced degree of knee pain after being adjusted for the above covariates (β: −0.48, 95% CI: −0.91 to −0.05, p = 0.029). There was a significantly accumulative effect of MET use on the reduced risk of TKA. Conclusion: MET can be a potential therapeutic option for OA. Further clinical trials are needed to determine if MET can reduce the risk of TKA and the severity of knee pain in metabolic-associated OA patients. Full article

(This article belongs to the Special Issue Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease)

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14 pages, 1021 KiB

Open AccessArticle

Macroscopic Synovial Inflammation Correlates with Symptoms and Cartilage Lesions in Patients Undergoing Arthroscopic Partial Meniscectomy: A Clinical Study

by Eleonora Olivotto, Giovanni Trisolino, Elisa Belluzzi, Antonello Lazzaro, Alessandro Strazzari, Assunta Pozzuoli, Augusto Cigolotti, Pietro Ruggieri, Andrea Evangelista, Francesca Ometto, Stefano Stallone, Steven R. Goldring, Mary B. Goldring, Roberta Ramonda, Brunella Grigolo and Marta Favero

J. Clin. Med. 2022, 11(15), 4330; https://doi.org/10.3390/jcm11154330 - 26 Jul 2022

Cited by 12 | Viewed by 1540

Abstract

Background: The aim of the study was to examine the relationship among patients’ characteristics, intraoperative pathology and pre/post-operative symptoms in a cohort of patients undergoing arthroscopic partial meniscectomy for symptomatic meniscal tears. Methods: Clinical data were collected (age, sex, body mass index, time to surgery, trauma). Intraoperative cartilage pathology was assessed with Outerbridge score. Meniscal tears were graded with the ISAKOS classification. Synovial inflammation was scored using the Macro-score. Patient symptoms were assessed pre/post-operatively using the KOOS instrument. Results: In the series of 109 patients (median age 47 years), 50% of the meniscal tears were traumatic; 85% of patients showed mild to moderate synovitis; 52 (47.7%) patients had multiple cartilage defects and 31 (28.4%) exhibited a single focal chondral lesion. Outerbridge scores significantly correlated with patient age, BMI and synovial inflammation. There was a correlation between severity of chondral pathology and high-grade synovial hyperplasia. Pre-operative KOOS correlated with BMI, meniscal degenerative changes and symptom duration. Obesity, time to surgery, presence of high-grade synovial hyperplasia and high-grade cartilage lesions were independent predictors of worse post-operative pain and function. Conclusion: We demonstrated that pre-operative symptoms and post-operative outcomes correlate with synovitis severity and cartilage pathology, particularly in old and obese patients that underwent arthroscopic partial meniscectomy. Importantly, patients with a degenerative meniscal pattern and with longer time to surgery experienced more severe cartilage damage and, consequentially, pain and dysfunction. These findings are fundamental to identify patients suitable for earlier interventions. Full article

(This article belongs to the Special Issue Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease)

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13 pages, 2167 KiB

Open AccessArticle

Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes

by Olivier Malaise, Geneviève Paulissen, Céline Deroyer, Federica Ciregia, Christophe Poulet, Sophie Neuville, Zelda Plener, Christophe Daniel, Philippe Gillet, Chantal Lechanteur, Jean-Marc Brondello, Dominique de Seny and Michel Malaise

J. Clin. Med. 2021, 10(22), 5331; https://doi.org/10.3390/jcm10225331 - 16 Nov 2021

Cited by 4 | Viewed by 2107

Abstract

Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks and senescence induction in fibroblast-like synoviocytes (FLS) from OA patients and mesenchymal stem cells (MSC). Methods: Cellular senescence was assessed via the proliferation rate, β-galactosidase staining, DNA damage and CKI expression (p21, p16^INK4A). Experimental senescence was induced by irradiation. Results: The GC prednisolone did not induce an apparent senescence phenotype in FLS, with even higher proliferation, no accumulation of β-galactosidase-positive cells nor DNA damage and reduction in p21mRNA, only showing the enhancement of p16^INK4A. Prednisolone did not modify experimental senescence induction in FLS, with no modulation of any senescence parameters. Moreover, prednisolone did not induce a senescence phenotype in MSC: despite high β-galactosidase-positive cells, no reduction in proliferation, no DNA damage and no CKI enhancement was observed. Conclusions: We provide reassuring in vitro data about the use of GC regarding cellular senescence involvement in OA: the GC prednisolone did not induce a senescent phenotype in OA FLS (the proliferation ratio was even higher) and in MSC and did not worsen cellular senescence establishment. Full article

(This article belongs to the Special Issue Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease)

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17 pages, 1379 KiB

Open AccessArticle

Attenuative Effects of Platelet-Rich Plasma on 30 kDa Fibronectin Fragment-Induced MMP-13 Expression Associated with TLR2 Signaling in Osteoarthritic Chondrocytes and Synovial Fibroblasts

by Hsien-Tsung Lu, Jeng-Wei Lu, Chian-Her Lee, Yi-Jen Peng, Herng-Sheng Lee, You-Hsiang Chu, Yi-Jung Ho, Feng-Cheng Liu, Pei-Hung Shen and Chih-Chien Wang

J. Clin. Med. 2021, 10(19), 4496; https://doi.org/10.3390/jcm10194496 - 29 Sep 2021

Cited by 3 | Viewed by 2054

Abstract

Proteolytic fragments of fibronectin can have catabolic effects on cartilage, menisci, and synovium. Previous studies have reported that Toll-like receptor (TLR) signaling pathways might be associated with joint inflammation and joint destruction. Platelet-rich plasma (PRP) is increasingly being used to treat a range of joint conditions; however, it has yet to be determined whether PRP influences fibronectin fragment (FN-f) procatabolic activity and TLRs. In this study, human primary culture cells were treated with 30 kDa FN-f with/without PRP co-incubation, and then analyzed using real-time PCR to determine gene expression levels in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts. Protein levels were evaluated by Western immunoblotting. This study observed an increase in the protein expression of matrix metalloproteinases (MMPs), Toll-like receptor 2 (TLR2), nitric oxide synthase 2 (NOS2), prostaglandin-endoperoxide synthase (PTGS2), and cyclooxygenase 2 (COX2) in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts following insult with 30 kDa FN-f. Upregulation of these genes was significantly attenuated by PRP treatment. TLR2 and matrix metalloproteinase 13 (MMP-13) were also significantly attenuated by cotreatment with 30 kDa FN-f + PRP + TLR2 inhibitor. PRP treatment was shown to attenuate the 30 kDa FN-f-induced MMP-13 expression associated with the decreased expression of TLR2 in osteoarthritic chondrocytes and synovial fibroblasts. PRP treatment was also shown to attenuate procatabolic activity associated with MMP-13 expression via the TLR2 signaling pathway. Full article

(This article belongs to the Special Issue Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease)

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Review

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21 pages, 1333 KiB

Open AccessReview

Osteoarthritis: Pathogenesis, Animal Models, and New Regenerative Therapies

by Tomasz Szponder, Michał Latalski, Anna Danielewicz, Katarzyna Krać, Aleksandra Kozera, Beata Drzewiecka, Dominika Nguyen Ngoc, Dominika Dobko and Joanna Wessely-Szponder

J. Clin. Med. 2023, 12(1), 5; https://doi.org/10.3390/jcm12010005 - 20 Dec 2022

Cited by 25 | Viewed by 4279

Abstract

Osteoarthritis (OA) is a chronic, progressive, multifactorial disease resulting in a progressive loss of articular cartilage structure and function that is most common in middle-aged and older patients. OA is involved in the loss of extracellular matrix and cartilage as well as cell number decreases within the matrix, especially in the further stages of the disease. The immune system plays a pivotal role in the pathomechanism of this condition. Both humoral and cellular mediators contribute to cartilage destruction, abnormal bone remodeling, synovitis, and joint effusion. The increasing prevalence of this disease has led to a growing interest in using animal models as the primary way to broaden the knowledge of the pathogenesis of OA and possible therapies at each stage of disease development. This review aims to describe the signs, pathogenesis, and classification of OA as well as discuss the advantages and disadvantages of some animal models. The currently used treatment methods include mesenchymal stem cells, exosomes, gene therapies, and blood-derived products. In addition, exogenous growth factors, platelet-rich plasma (PRP), platelet lysate, and autologous conditioned serum (ACS) are discussed with the application of tissue engineering techniques and biomaterials. Full article

(This article belongs to the Special Issue Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease)

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16 pages, 1959 KiB

Open AccessReview

Relative Efficacy and Safety of Anti-Inflammatory Biologic Agents for Osteoarthritis: A Conventional and Network Meta-Analysis

by Yang Li, Yiying Mai, Peihua Cao, Xin Wen, Tianxiang Fan, Xiaoshuai Wang, Guangfeng Ruan, Su’an Tang, Changhai Ding and Zhaohua Zhu

J. Clin. Med. 2022, 11(14), 3958; https://doi.org/10.3390/jcm11143958 - 7 Jul 2022

Cited by 12 | Viewed by 2622

Abstract

Previous studies have consistently revealed that both local and systemic inflammations are the key to the onset and progression of osteoarthritis (OA). Thus, anti-inflammatory biologic agents could potentially attenuate the progression of OA. We conducted this meta-analysis to examine the efficacy and safety of ant-inflammatory biologic agents among OA patients. Methods: Five databases were searched for randomized controlled trials (RCTs) comparing biologics with placebo or each other in OA patients. Data of pain, physical function, stiffness, and adverse events (AEs) were extracted for a conventional and a Bayesian network meta-analysis. Results: 15 studies with data for 1566 patients were analyzed. In the conventional meta-analysis, etanercept (SMD −0.47; 95% CI −0.89, −0.05) and infliximab (SMD −2.04; CI −2.56, −1.52) were superior to placebo for knee pain. In the network meta-analysis, infliximab was superior to all the other biologic agents in improving pain (vs. hyaluronic acid (SMD −22.95; CI −34.21, −10.43), vs. adalimumab (SMD −21.71; CI −32.65, −11.00), vs. anakinra (SMD −24.63; CI −38.79, −10.05), vs. canakinumab (SMD −32.83; CI −44.45, −20.68), vs. etanercept (SMD −18.40; CI −29.93, −5.73), vs. lutikizumab (SMD −25.11; CI −36.47, −14.78), vs. naproxen (SMD −30.16; CI −41.78, −17.38), vs. tocilizumab (SMD −24.02; CI −35.63, −11.86) and vs. placebo (SMD −25.88; CI −34.87, −16.60)). No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. Conclusions: The findings suggest that infliximab may relieve pain more than other biological agents in OA patients. No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. The results must be interpreted cautiously; therefore, further randomized controlled trials are warranted. Full article

(This article belongs to the Special Issue Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease)

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Other

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7 pages, 660 KiB

Open AccessOpinion

Prevalence of Sarcopenia in Knee Osteoarthritis: A Systematic Review and Meta-Analysis

by Francesco Pegreffi, Alice Balestra, Orazio De Lucia, Lee Smith, Mario Barbagallo and Nicola Veronese

J. Clin. Med. 2023, 12(4), 1532; https://doi.org/10.3390/jcm12041532 - 15 Feb 2023

Cited by 15 | Viewed by 2525

Abstract

An association between knee osteoarthritis (OA) and sarcopenia has been proposed, but the evidence is controversial, with the recent literature showing disparate results. Therefore, we aimed to perform a systematic review and meta-analysis to evaluate the prevalence of sarcopenia in knee OA patients compared to people not affected by this condition. We searched several databases until 22 February 2022. The data regarding prevalence were summarized using odds ratios (ORs) with their 95% confidence intervals (CIs). Among the 504 papers initially screened, 4 were included for a total of 7495 participants with a mean age of 68.4 years, who were mainly females (72.4%). The prevalence of sarcopenia in people with knee OA was 45.2%, whilst, in the controls, it was 31.2%. Pooling the data of the studies included that the prevalence of sarcopenia in knee OA was more than two times higher than in the control group (OR = 2.07; 95%CI: 1.43–3.00; I² = 85%). This outcome did not suffer any publication bias. However, after removing an outlier study, the recalculated OR was 1.88. In conclusion, the presence of sarcopenia in knee OA patients was high, affecting one person in every two persons and was higher than in the control groups included. Full article

(This article belongs to the Special Issue Osteoarthritis: Novel Advances in the Understanding and Therapeutic Management of the Disease)

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