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Osteoarthritis: From Molecular Mechanism to Novel Therapy

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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: 20 February 2025 | Viewed by 8535

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Dr. Berardo Di Matteo

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Center for Functional and Biologic Reconstruction of the Knee, Humanitas Clinical and Research Center, Via Manzoni 113, 20089 Rozzano, Milan, Italy
Interests: cartilage; stem cells; scaffold; growth factors; TKR; CAS; orthobiology; ACL; meniscus transplant
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Dear Colleagues,

Osteoarthritis (OA) is the most common form of joint disease that appears in more than 10% of the world population and affects almost everyone over 65. As a consequence of the increasing longevity and obesity Worldwide especially in Western Countries, the economic and social burden of OA is rapidly and dramatically increasing affecting the quality of life of affected individuals and imposing enormous diagnostic, treatment, sick leave, rehabilitation, and early retirement costs on healthcare systems.

OA is not just an articular cartilage disease; it can be considered an organ failure of the entire joint with other abnormalities, especially of the bones, ligaments, synovium, and joint capsule. Furthermore, OA is characterized by its extraordinary interpatient variability both clinically and structurally which increases the complexity of OA and the ongoing difficulties in therapies. And no specific diagnostic biomarkers have been identified for OA that can identify the disease at its earliest stages.

With substantial advances in molecular biology, genetics, genomics, and animal models of OA, OA has evolved into a disease in which systemic inflammation and the immune system significantly alter the disease, also classifying it as an inflammatory disease. Consequently, disease-modifying drugs for osteoarthritis (DMOADS) are rapidly being developed, with attention shifting to novel targets including transcription factors, growth factors, and receptors. This Special Issue aims to help foster the advancement of the field of OA research and to disseminate new discoveries and information related to OA diagnosis, and therapy.

Dr. Berardo Di Matteo
Guest Editor

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Keywords

osteoarthritis
joint inflammation
cartilage and chondrocyte function
cartilage regeneration and repair
post-traumatic osteoarthritis
synovium

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Published Papers (5 papers)

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20 pages, 12378 KiB

Open AccessArticle

Distinctiveness of Femoral and Acetabular Mesenchymal Stem and Progenitor Populations in Patients with Primary and Secondary Hip Osteoarthritis Due to Developmental Dysplasia

by Mihovil Plečko, Nataša Kovačić, Danka Grčević, Alan Šućur, Andreja Vukasović Barišić, Tea Duvančić, Ivan Bohaček and Domagoj Delimar

Int. J. Mol. Sci. 2024, 25(10), 5173; https://doi.org/10.3390/ijms25105173 - 9 May 2024

Viewed by 996

Abstract

Primary hip osteoarthritis (pOA) develops without an apparent underlying reason, whereas secondary osteoarthritis arises due to a known cause, such as developmental dysplasia of the hips (DDH-OA). DDH-OA patients undergo total hip arthroplasty at a much younger age than pOA patients (50.58 vs. 65 years in this study). Recently, mesenchymal stem and progenitor cells (MSPCs) have been investigated for the treatment of osteoarthritis due to their immunomodulatory and regenerative potential. This study identified cells in subchondral bone expressing common MSPC markers (CD10, CD73, CD140b, CD146, CD164, CD271, GD2, PDPN) in vivo and compared the proportions of these populations in pOA vs. DDH-OA, further correlating them with clinical, demographic, and morphological characteristics. The differences in subchondral morphology and proportions of non-hematopoietic cells expressing MSPC markers were noted depending on OA type and skeletal location. Bone sclerosis was more prominent in the pOA acetabulum (Ac) in comparison to the DDH-OA Ac and in the pOA Ac compared to the pOA femoral head (Fh). Immunophenotyping indicated diagnosis-specific differences, such as a higher proportion of CD164+ cells and their subsets in DDH-OA, while pOA contained a significantly higher proportion of CD10+ and GD2+ cells and subsets, with CD271+ being marginally higher. Location-specific differences showed that CD271+ cells were more abundant in the Fh compared to the Ac in DDH-OA patients. Furthermore, immunohistochemical characterization of stromal bone-adjacent cells expressing MSPC markers (CD10, CD164, CD271, GD2) in the Ac and Fh compartments was performed. This research proved that immunophenotype profiles and morphological changes are both location- and disease-specific. Furthermore, it provided potentially effective targets for therapeutic strategies. Future research should analyze the differentiation potential of subsets identified in this study. After proper characterization, they can be selectively targeted, thus enhancing personalized medicine approaches in joint disease management. Full article

(This article belongs to the Special Issue Osteoarthritis: From Molecular Mechanism to Novel Therapy)

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15 pages, 5237 KiB

Open AccessArticle

The Combination of Glucocorticoids and Hyaluronic Acid Enhances Efficacy in IL-1β/IL-17-Treated Bovine Osteochondral Grafts Compared with Individual Application

by Christoph Bauer, Lukas B. Moser, Daniela Kern, Vivek Jeyakumar and Stefan Nehrer

Int. J. Mol. Sci. 2023, 24(18), 14338; https://doi.org/10.3390/ijms241814338 - 20 Sep 2023

Cited by 3 | Viewed by 1546

Abstract

Patients with knee osteoarthritis often receive glucocorticoid (GC) or hyaluronic acid (HA) injections to alleviate symptoms. This study evaluated the impact of Triamcinolone Hexacetonide (a GC), HA, and a combination of both on bovine osteochondral grafts exposed to IL-1β and IL-17 in an ex vivo culture. Metabolic activity increased with GC treatment. GCs and GCs/HA counteracted cytokine effects, with gene expressions similar to untreated controls, while HA alone did not. However, HA improved the coefficient of friction after two weeks. The highest friction values were observed in GC-containing and cytokine-treated groups. Cytokine treatment reduced tissue proteoglycan content, which HA could mitigate, especially in the GC/HA combination. This combo also effectively controlled proteoglycan release, supported by reduced sGAG release. Cytokine treatment led to surface cell death, while GCs, HA, or their combination showed protective effects against inflammation. The GC/HA combination had the best overall results, suggesting its potential as a superior treatment option for osteoarthritis. Full article

(This article belongs to the Special Issue Osteoarthritis: From Molecular Mechanism to Novel Therapy)

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15 pages, 4966 KiB

Open AccessArticle

Propolis as a Potential Therapeutic Agent to Counteract Age-Related Changes in Cartilage: An In Vivo Study

by Consuelo Arias, Bélgica Vásquez and Luis A. Salazar

Int. J. Mol. Sci. 2023, 24(18), 14272; https://doi.org/10.3390/ijms241814272 - 19 Sep 2023

Cited by 2 | Viewed by 1911

Abstract

Aging is intricately linked to chronic low-grade systemic inflammation, which plays a significant role in various age-related conditions, including osteoarthritis (OA). The aging process significantly influences the development of OA due to alterations in cartilage composition, reduced proteoglycan content, dysregulation of growth factor signaling, and heightened oxidative stress. Propolis, a natural product renowned for its potent antioxidant and anti-inflammatory properties, has the potential to mitigate age-induced changes in cartilage. The primary objective of this study was to rigorously assess the impact of in vivo propolis treatment on the histopathological characteristics of knee articular cartilage in senescent rats. This study involved a cohort of twenty male Sprague–Dawley rats, randomly allocated into four distinct groups for comparative analysis: YR (control group consisting of young rats), SR (senescent rats), SR-EEP (senescent rats treated with an ethanolic extract of propolis, EEP), and SR-V (senescent rats administered with a control vehicle). This study employed comprehensive histological and stereological analyses of knee articular cartilage. Propolis treatment exhibited a significant capacity to alleviate the severity of osteoarthritis, enhance the structural integrity of cartilage, and augment chondrocyte density. These promising findings underscore the potential of propolis as a compelling therapeutic agent to counteract age-related alterations in cartilage and, importantly, to potentially forestall the onset of osteoarthritis. Full article

(This article belongs to the Special Issue Osteoarthritis: From Molecular Mechanism to Novel Therapy)

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16 pages, 2265 KiB

Open AccessArticle

Hypoxia Preconditioned Serum (HPS) Promotes Proliferation and Chondrogenic Phenotype of Chondrocytes In Vitro

by Jun Jiang, Jannat Altammar, Xiaobin Cong, Lukas Ramsauer, Vincent Steinbacher, Ulf Dornseifer, Arndt F. Schilling, Hans-Günther Machens and Philipp Moog

Int. J. Mol. Sci. 2023, 24(13), 10441; https://doi.org/10.3390/ijms241310441 - 21 Jun 2023

Cited by 2 | Viewed by 1808

Abstract

Autologous chondrocyte implantation (ACI) for the treatment of articular cartilage defects remains challenging in terms of maintaining chondrogenic phenotype during in vitro chondrocyte expansion. Growth factor supplementation has been found supportive in improving ACI outcomes by promoting chondrocyte redifferentiation. Here, we analysed the chondrogenic growth factor concentrations in the human blood-derived secretome of Hypoxia Preconditioned Serum (HPS) and assessed the effect of HPS-10% and HPS-40% on human articular chondrocytes from osteoarthritic cartilage at different time points compared to normal fresh serum (NS-10% and NS-40%) and FCS-10% culture conditions. In HPS, the concentrations of TGF-beta1, IGF-1, bFGF, PDGF-BB and G-CSF were found to be higher than in NS. Chondrocyte proliferation was promoted with higher doses of HPS (HPS-40% vs. HPS-10%) and longer stimulation (4 vs. 2 days) compared to FCS-10%. On day 4, immunostaining of the HPS-10%-treated chondrocytes showed increased levels of collagen type II compared to the other conditions. The promotion of the chondrogenic phenotype was validated with quantitative real-time PCR for the expression of collagen type II (COL2A1), collagen type I (COL1A1), SOX9 and matrix metalloproteinase 13 (MMP13). We demonstrated the highest differentiation index (COL2A1/COL1A1) in HPS-10%-treated chondrocytes on day 4. In parallel, the expression of differentiation marker SOX9 was elevated on day 4, with HPS-10% higher than NS-10/40% and FCS-10%. The expression of the cartilage remodelling marker MMP13 was comparable across all culture conditions. These findings implicate the potential of HPS-10% to improve conventional FCS-based ACI culture protocols by promoting the proliferation and chondrogenic phenotype of chondrocytes during in vitro expansion. Full article

(This article belongs to the Special Issue Osteoarthritis: From Molecular Mechanism to Novel Therapy)

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13 pages, 747 KiB

Open AccessBrief Report

Ethanolic Extract of Propolis Modulates Autophagy-Related microRNAs in Osteoarthritic Chondrocytes

by Consuelo Arias and Luis A. Salazar

Int. J. Mol. Sci. 2023, 24(19), 14767; https://doi.org/10.3390/ijms241914767 - 30 Sep 2023

Cited by 4 | Viewed by 1616

Abstract

Osteoarthritis is a multifactorial joint disease characterized by degeneration, and aging stands as a significant risk factor. Autophagy, a crucial cellular homeostasis mechanism, is influenced by aging and closely linked to cartilage health. This correlation between autophagy, cell death, and OA underscores its relevance in disease progression. MicroRNAs have emerged as autophagy regulators, with miRNA-based interventions showing promise in preclinical models. Remarkably, the ethanolic extract of propolis exhibits positive effects on autophagy-related proteins and healthy cartilage markers in an in vitro osteoarthritis model. The aim of this brief report was to evaluate through in silico analysis and postulate five microRNAs that could regulate autophagy proteins (AKT1, ATG5, and LC3) and assess whether the ethanolic extract of propolis could regulate the expression of these microRNAs. Among the examined miRNAs (miR-19a, miR-125b, miR-181a, miR-185, and miR-335), the ethanolic extract of propolis induced significant changes in four of them. Specifically, miR-125b responded to EEP by counteracting IL-1β-induced effects, while miR-181a, miR-185, and miR-335 exhibited distinct patterns of expression under EEP treatment. These findings unveil a potential link between miRNAs, EEP, and autophagy modulation in OA, offering promising therapeutic insights. Nevertheless, further validation and clinical translation are warranted to substantiate these promising observations. Full article

(This article belongs to the Special Issue Osteoarthritis: From Molecular Mechanism to Novel Therapy)

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