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Osteoarthritis Biomarkers, Diagnosis and Treatments
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Osteoarthritis Biomarkers, Diagnosis and Treatments

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 9033

Special Issue Editor

Prof. Hechmi Toumi

E-Mail Website
Guest Editor
Department of Rheumatology, Translational Medicine Research Platform, PRIMMO, Regional Hospital of Orleans, 45067 Orleans, France
Interests: Arthritis & osteoarthritis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For several decades, osteoarthritis (OA) has remained the most common cause of disability in older adults. To date, clinicians face often difficulties assisting their patients as no registered disease-modifying OA drugs exist, and only symptomatic treatments are available. In fact, multiple joint tissues are involved in OA pathophysiology; cartilage was often the focus of research and long thought to play a primary role. However, although cartilage is usually impaired, it is an aneural tissue and pain would be more related to synovium and subchondral bones.

The relationship between osteoarthritis, cartilage degeneration and bone is strong and complex. Research on the mechanisms of osteoarthritis can help us to determine the molecular biology, biochemical, and biomechanical mechanisms involved in the degeneration, repair and regeneration of joints. New targets and compounds for these targets are currently under investigation.

This Special Issue aims to focus on the most recent research conducted in the domain of molecular mechanisms that impact OA repair and treatments. Experimental studies, as well as clinical submissions with biomolecular experiments, are within the scope of our Special Issue and are welcomed for submission, in particular (1) disease-modifying OA drugs, (2) advanced cell treatments for osteoarthritis, (3) changes in cells’ biological mechanisms resulting from osteoarthritis; (4) osteoarthritis and chemical and biomolecular engineering.

All authors are invited to send their research related to the topic of our Special Issue, including both original and review articles, to be assessed and included in the peer review process of our journal.

Prof. Hechmi Toumi
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • degenerative joint disease
  • biomarkers
  • diagnosis
  • treatments

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Published Papers (5 papers)

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Research

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11 pages, 894 KiB  
Article
The Effect of Intravascular Laser Irradiation of Blood on Serum Biomarkers and Clinical Outcome in Knee Osteoarthritis Patients: A Double-Blind Randomized Control Trial
by Yu-Chi Su, Yu-Ping Shen, Chih-Ya Chang, Ke-Ting Pan, Shih-Ming Huang and Liang-Cheng Chen
Int. J. Mol. Sci. 2024, 25(24), 13608; https://doi.org/10.3390/ijms252413608 - 19 Dec 2024
Viewed by 1094
Abstract
Knee osteoarthritis (OA) is a prevalent degenerative joint disease globally, causing pain, stiffness, and disability. Intravascular laser irradiation of blood (ILIB) has been used for chronic pain and musculoskeletal disease. However, evidence on the clinical benefits and serum biomarkers post-ILIB therapy in knee [...] Read more.
Knee osteoarthritis (OA) is a prevalent degenerative joint disease globally, causing pain, stiffness, and disability. Intravascular laser irradiation of blood (ILIB) has been used for chronic pain and musculoskeletal disease. However, evidence on the clinical benefits and serum biomarkers post-ILIB therapy in knee OA is insufficient. We designed a double-blind randomized controlled trial to evaluate the clinical and biological outcomes of ILIB therapy for knee OA. Seventeen patients with knee OA were randomly assigned to the ILIB and control groups. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Scale, visual analog scale, and biomarker analysis of interleukin (IL)-6, IL-13, IL-1β, epidermal growth factor, macrophage inflammatory protein-1β, and eotaxin. The measurements were performed at baseline and three days, one month, and three months post-intervention. The ILIB group showed a significant improvement in the WOMAC-pain score at one month of follow-up than the control group. IL-1β levels reduced significantly on day three, one month, and three months, and IL-13 levels reduced on day three and three months during follow-up in the ILIB group. ILIB therapy reduced knee OA pain for one month and significantly reduced serum IL-1β and IL-13 levels, suggesting potential for pain management. Full article
(This article belongs to the Special Issue Osteoarthritis Biomarkers, Diagnosis and Treatments)
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14 pages, 2280 KiB  
Article
TNFα-Induced Inflammation Model—Evaluation of Concentration and Passage-Dependent Effects on Bovine Chondrocytes
by Robert Ossendorff, Su Wang, Sarah Kurth, Max Jaenisch, Elio Assaf, Andreas C. Strauss, Damien Bertheloot, Kristian Welle, Christof Burger, Dieter C. Wirtz and Frank A. Schildberg
Int. J. Mol. Sci. 2024, 25(17), 9136; https://doi.org/10.3390/ijms25179136 - 23 Aug 2024
Cited by 1 | Viewed by 1294
Abstract
Inflammation models are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis. TNFα (tumor necrosis factor alpha) plays an important role in the inflammatory process. Current inflammation models lack uniformity and make comparisons difficult. Therefore, this study aimed to [...] Read more.
Inflammation models are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis. TNFα (tumor necrosis factor alpha) plays an important role in the inflammatory process. Current inflammation models lack uniformity and make comparisons difficult. Therefore, this study aimed to systematically investigate whether the effects of TNFα are concentration-dependent and whether chondrocyte expansion has an effect on the inflammatory model. Bovine chondrocytes were enzymatically isolated, expanded to passages 1–3, and transferred into a 3D pellet culture. Chondrocyte pellets were stimulated with recombinant bovine TNFα at different concentrations for 48 h to induce inflammation. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP)), catabolic (matrix metalloproteinases (MMP3, MMP13)), dedifferentiation (collagen 1) markers, inflammation markers (interleukin-6 (IL-6), nuclear factor kappa B (NFkB), cyclooxygenase-2 (COX), prostaglandin-E-synthase-2 (PTGES2)), and the apoptosis marker caspase 3 was determined. At the protein level, concentrations of IL-6, nitric oxide (NO), and sulfated glycosaminoglycans (GAG) were evaluated. Statistical analysis was performed using the independent t-test, and significance was defined as p < 0.05. In general, TNFα caused a decrease in anabolic markers and an increase in the expression of catabolic and inflammatory markers. There was a concentration-dependent threshold of 10 ng/mL to induce significant inflammatory effects. Most of the markers analyzed showed TNFα concentration-dependent effects (COMP, PRG4, AGN, Col1, MMP3, and NFkB). There was a statistical influence of selected gene expression markers from different passages on the TNFα chondrocyte inflammation model, including Col2, MMP13, IL-6, NFkB, COX2, and PTGES2. Considering the expression of collagen 2 and MMP3, passage 3 chondrocytes showed a higher sensitivity to TNFα stimulation compared to passages 1 and 2. On the other hand, MMP13, IL-6, NFkB, and caspase 3 gene expression were lower in P3 chondrocytes compared to the other passages. On the protein level, inflammatory effects showed a similar pattern, with cytokine effects starting at 10 ng/mL and differences between the passages. TNFα had a detrimental effect on cartilage, with a clear threshold observed at 10 ng/mL. Although TNFα effects showed concentration-dependent patterns, this was not consistent for all markers. The selected passage showed a clear influence, especially on inflammation markers. Further experiments were warranted to explore the effects of TNFα concentration and passage in long-term stimulation. Full article
(This article belongs to the Special Issue Osteoarthritis Biomarkers, Diagnosis and Treatments)
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16 pages, 23556 KiB  
Article
The Therapeutic Potential of Intra-Articular Injection of Synthetic Deer Antler Peptides in a Rat Model of Knee Osteoarthritis
by Yu-Chou Hung, Li-Jin Chen, Jen-Hung Wang, Tsung-Jung Ho, Guo-Fang Tseng and Hao-Ping Chen
Int. J. Mol. Sci. 2024, 25(11), 6041; https://doi.org/10.3390/ijms25116041 - 30 May 2024
Cited by 1 | Viewed by 2413
Abstract
Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen and glycosamino-glycan in vitro. This study investigated the peptide mixture’s pain relief and chondroprotective effect in a rat model of [...] Read more.
Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen and glycosamino-glycan in vitro. This study investigated the peptide mixture’s pain relief and chondroprotective effect in a rat model of collagenase-induced osteoarthritis. Thirty-six adult male Sprague–Dawley rats were divided into three groups: control (saline), positive control (hyaluronic acid), and ex-perimental (peptides). Intra-articular collagenase injections were administered on days 1 and 4 to induce osteoarthritis in the left knees of the rats. Two injections of saline, hyaluronic acid, or the peptides were injected into the same knees of each corresponding group at the beginning of week one and two, respectively. Joint swelling, arthritic pain, and histopathological changes were evaluated. Injection of the peptides significantly reduced arthritic pain compared to the control group, as evidenced by the closer-to-normal weight-bearing and paw withdrawal threshold test results. Histological analyses showed reduced cartilage matrix loss and improved total cartilage degeneration score in the experimental versus the control group. Our findings suggest that intra-articular injection of synthetic deer antler peptides is a promising treatment for osteoarthritis. Full article
(This article belongs to the Special Issue Osteoarthritis Biomarkers, Diagnosis and Treatments)
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Review

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25 pages, 2000 KiB  
Review
The Role of Adipokines between Genders in the Pathogenesis of Osteoarthritis
by Alessio Economou, Ilenia Mallia, Antonella Fioravanti, Stefano Gentileschi, Francesca Nacci, Silvia Bellando Randone, Gemma Lepri and Serena Guiducci
Int. J. Mol. Sci. 2024, 25(19), 10865; https://doi.org/10.3390/ijms251910865 - 9 Oct 2024
Cited by 2 | Viewed by 1923
Abstract
Osteoarthritis (OA) is a chronic, progressive, degenerative joint disease characterized by joint pain, stiffness, and limited movement. It presents significant intra- and inter-individual variability—in particular, between genders. Recent research has increasingly focused on the role of adipokines—especially leptin, adiponectin, and resistin—in the development [...] Read more.
Osteoarthritis (OA) is a chronic, progressive, degenerative joint disease characterized by joint pain, stiffness, and limited movement. It presents significant intra- and inter-individual variability—in particular, between genders. Recent research has increasingly focused on the role of adipokines—especially leptin, adiponectin, and resistin—in the development of OA. Adipokines, peptide hormones primarily secreted by adipose tissue, are involved in crucial physiological processes related to metabolism and immunity. They can also impact bone and cartilage turnover by interacting with joint cells such as osteoblasts, osteoclasts, chondrocytes, and mesenchymal stem cells, thereby linking inflammation with bone cartilage homeostasis. This review aims to elucidate the structure and functions of various adipokines, their serum and synovial levels, and their association with clinical presentation and radiographic progression in OA patients, with a focus on differences between sexes. A narrative literature review was conducted using three databases specifically analyzing sex differences. OA patients generally show elevated serum and synovial levels of leptin, chemerin, and visfatin, as well as high plasma levels of resistin and visfatin. In contrast, synovial levels of adiponectin and omentin are reduced in OA patients compared to healthy individuals, with an inverse relationship to disease severity, suggesting a potential protective role. Resistin and leptin were positively correlated with pain severity and radiographic progression, while adiponectin’s role in OA remains controversial. Regarding sex differences, male OA patients exhibited higher serum levels of leptin, chemerin, and omentin compared to healthy controls, with a positive correlation to the BMI and estrogen levels, potentially explaining the sexual dimorphism observed in this condition. Studies on visfatin and lipocalin did not reveal significant differences in synovial or serum levels between the sexes. The role of resistin remains controversial. Adipokines influence the joint microenvironment and contribute to the progression of osteoarthritis (OA). However, the precise biological mechanisms are not yet fully understood due to the complex interactions between the metabolic, mechanical, and immune systems. Further research is needed to clarify their roles in OA and to identify targeted therapies for managing this degenerative disease. Full article
(This article belongs to the Special Issue Osteoarthritis Biomarkers, Diagnosis and Treatments)
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19 pages, 4720 KiB  
Review
TNFα-Related Chondrocyte Inflammation Models: A Systematic Review
by Su Wang, Sarah Kurth, Christof Burger, Dieter C. Wirtz, Frank A. Schildberg and Robert Ossendorff
Int. J. Mol. Sci. 2024, 25(19), 10805; https://doi.org/10.3390/ijms251910805 - 8 Oct 2024
Cited by 1 | Viewed by 1453
Abstract
Tumor necrosis factor alpha (TNFα), as a key pro-inflammatory cytokine, plays a central role in joint diseases. In recent years, numerous models of TNFα-induced cartilage inflammation have been developed. However, due to the significant differences between these models and the lack of consensus [...] Read more.
Tumor necrosis factor alpha (TNFα), as a key pro-inflammatory cytokine, plays a central role in joint diseases. In recent years, numerous models of TNFα-induced cartilage inflammation have been developed. However, due to the significant differences between these models and the lack of consensus in their construction, it becomes difficult to compare the results of different studies. Therefore, we summarized and compared these models based on important parameters for model construction, such as cell source, cytokine concentration, stimulation time, mechanical stimulation, and more. We attempted to analyze the advantages and disadvantages of each model and provide a compilation of the analytical methods used in previous studies. Currently, TNFα chondrocyte inflammation models can be categorized into four main types: monolayer-based, construct-based, explant-based TNFα chondrocyte inflammation models, and miscellaneous TNFα chondrocyte inflammation models. The most commonly used models were the monolayer-based TNFα chondrocyte inflammation models (42.86% of cases), with 10 ng/mL TNFα being the most frequently used concentration. The most frequently used chondrocyte cell passage is passage 1 (50%). Human tissues were most frequently used in experiments (51.43%). Only five articles included models with mechanical stimulations. We observed variations in design conditions between different models. This systematic review provides the essential experimental characteristics of the available chondrocyte inflammation models with TNFα, and it provides a platform for better comparison between existing and new studies in this field. It is essential to perform further experiments to standardize each model and to find the most appropriate experimental parameters. Full article
(This article belongs to the Special Issue Osteoarthritis Biomarkers, Diagnosis and Treatments)
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