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Pharmaceuticals
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Pharmacological Treatments for Osteoarthritis
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Pharmacological Treatments for Osteoarthritis

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 January 2024) | Viewed by 6268

Special Issue Editors

Dr. Juliana Priscila Vago

E-Mail Website
Guest Editor
Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands
Interests: arthritis; macrophage polarization; pro-resolving mediators; efferocytosis; resolution of inflammation
Prof. Dr. Flavio A. Amaral

E-Mail Website
Guest Editor
Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
Interests: arthritis; chemokine; resolution of inflammation; inflammatory pain
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Osteoarthritis (OA) is the most common form of arthritis, and it is one of the leading causes of disability worldwide. This disorder is characterized by severe degeneration of articular cartilage in load-bearing joints, including the knees, hips, and hands. For many years, OA was considered a ‘wear and tear’ disease, but recent studies have shown that signs of low-grade synovial inflammation affect 50-80% of patients, contributing to disease progression and symptoms. This disease has been considered the major cause of chronic pain in adults, becoming a substantial personal and socioeconomic burden. Thus far, no disease-modifying drugs are available to stop or slow its process. Symptoms alleviation and final joint replacement in the advanced disease stage are the main treatment options available. Efforts have been made to identify treatment options with the aim of developing more effective therapeutic strategies to treat OA. In this regard, the journal Pharmaceuticals invites authors to submit their original research and review articles on experimental and clinical studies. Topics consist of potential pharmacological therapies to treat OA, including potential disease-modifying OA drugs (DMOADs) and new therapies to relieve pain. The collection of manuscripts will be published as a Special Issue of the journal.

Dr. Juliana Priscila Vago
Prof. Dr. Flavio A. Amaral
Guest Editors

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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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
  • therapy
  • synovial inflammation
  • cartilage degradation
  • pain

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Published Papers (2 papers)

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Research

16 pages, 3156 KiB  
Article
Gas6/Axl Axis Activation Dampens the Inflammatory Response in Osteoarthritic Fibroblast-like Synoviocytes and Synovial Explants
by Juliana P. Vago, Natália Valdrighi, Esmeralda N. Blaney-Davidson, Daniel L. A. H. Hornikx, Margot Neefjes, María E. Barba-Sarasua, Nathalie G. M. Thielen, Martijn H. J. van den Bosch, Peter M. van der Kraan, Marije I. Koenders, Flávio A. Amaral and Fons A. J. van de Loo
Pharmaceuticals 2023, 16(5), 703; https://doi.org/10.3390/ph16050703 - 6 May 2023
Cited by 2 | Viewed by 2832
Abstract
Osteoarthritis (OA) is the most prevalent joint disease, and it is characterized by cartilage degeneration, synovitis, and bone sclerosis, resulting in swelling, stiffness, and joint pain. TAM receptors (Tyro3, Axl, and Mer) play an important role in regulating immune responses, clearing apoptotic cells, [...] Read more.
Osteoarthritis (OA) is the most prevalent joint disease, and it is characterized by cartilage degeneration, synovitis, and bone sclerosis, resulting in swelling, stiffness, and joint pain. TAM receptors (Tyro3, Axl, and Mer) play an important role in regulating immune responses, clearing apoptotic cells, and promoting tissue repair. Here, we investigated the anti-inflammatory effects of a TAM receptor ligand, i.e., growth arrest-specific gene 6 (Gas6), in synovial fibroblasts from OA patients. TAM receptor expression was determined in synovial tissue. Soluble Axl (sAxl), a decoy receptor for the ligand Gas6, showed concentrations 4.6 times higher than Gas6 in synovial fluid of OA patients. In OA fibroblast-like synoviocytes (OAFLS) exposed to inflammatory stimuli, the levels of sAxl in the supernatants were increased, while the expression of Gas6 was downregulated. In OAFLS under TLR4 stimulation by LPS (Escherichia coli lipopolysaccharide), the addition of exogenous Gas6 by Gas6-conditioned medium (Gas6-CM) reduced pro-inflammatory markers including IL-6, TNF-α, IL-1β, CCL2, and CXCL8. Moreover, Gas6-CM downregulated IL-6, CCL2, and IL-1β in LPS-stimulated OA synovial explants. Pharmacological inhibition of TAM receptors by a pan inhibitor (RU301) or by a selective Axl inhibitor (RU428) similarly abrogated Gas6-CM anti-inflammatory effects. Mechanistically, Gas6 effects were dependent on Axl activation, determined by Axl, STAT1, and STAT3 phosphorylation, and by the downstream induction of the suppressors of the cytokine signaling family (SOCS1 and SOCS3). Taken together, our results showed that Gas6 treatment dampens inflammatory markers of OAFLS and synovial explants derived from OA patients associated with SOCS1/3 production. Full article
(This article belongs to the Special Issue Pharmacological Treatments for Osteoarthritis)
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17 pages, 1250 KiB  
Article
How Effective Are Non-Operative Intra-Articular Treatments for Bone Marrow Lesions in Knee Osteoarthritis in Adults? A Systematic Review of Controlled Clinical Trials
by Alexander C. Kleinschmidt, Ambrish Singh, Salman Hussain, Gregory A. Lovell and Anna Wong Shee
Pharmaceuticals 2022, 15(12), 1555; https://doi.org/10.3390/ph15121555 - 14 Dec 2022
Cited by 1 | Viewed by 2470
Abstract
Knee osteoarthritis (KOA) is a progressive joint disease and a leading source of chronic pain and disability. OA-bone marrow lesions (BMLs) are a recognised aetiopathological feature of KOA. Several intra-articular injectable therapies are recommended and used for management of KOA. This systematic review [...] Read more.
Knee osteoarthritis (KOA) is a progressive joint disease and a leading source of chronic pain and disability. OA-bone marrow lesions (BMLs) are a recognised aetiopathological feature of KOA. Several intra-articular injectable therapies are recommended and used for management of KOA. This systematic review assessed the efficacy and safety of intra-articular therapies for improving OA-BMLs and reducing pain in adults with KOA. The study was conducted following registered review protocol (PROSPERO CRD42020189461) and six bibliographic databases, and two clinical trial registries were searched. We included eight randomised clinical trials involving 1294 participants, reported in 12 publications from 2016 to 2021. Two studies of sprifermin, one of autologous protein solution (APS) and one of high-dose TissueGene-C, reported a positive effect on OA-BMLs under 1-year follow-up. Two studies with corticosteroids reported mixed findings with no beneficial effect beyond 14 weeks of follow-up. One study assessing platelet-rich plasma found no significant improvement in OA-BMLs at 12 months follow-up. Knee pain was improved in two studies evaluating TissueGene-C and one study assessing APS; the remaining studies found no improvement in knee pain. Overall, we found mixed evidence on the efficacy of intra-articular therapy for improving OA-BMLs in KOA. Additional studies with long-term follow-up are needed to confirm the effect of various intra-articular therapies on OA-BMLs in KOA. Full article
(This article belongs to the Special Issue Pharmacological Treatments for Osteoarthritis)
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