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Molecular Mechanisms and Therapeutic Approaches to Osteoarthritis
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Molecular Mechanisms and Therapeutic Approaches to Osteoarthritis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 3728

Special Issue Editor

Dr. Masato Sato

E-Mail Website
Guest Editor
Department of Orthopedic Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan
Interests: osteoarthritis; cartilage repair; regeneration; platelet rich plasma; MSCs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Osteoarthritis is a common disease that affects 10% of the world’s population. Despite the fact that Osteoarthritis shortens the healthy life expectancy of many elderly people, its molecular mechanisms remain largely unknown and, therefore, preventive and therapeutic measures are still limited to symptomatic treatment. On the other hand, the development of disease-modifying drugs has been long-awaited. In recent years, attention has been focused on the development of point-of-care cells and drugs that are administered intra-articularly. Local rather than systemic administration is attractive from the standpoint of reduced side effects and drug delivery; so, the delivery of macromolecular agents, genes, nucleic acids, cells, and regenerative medicine are being developed.

This Special Issue, "Molecular Mechanisms and Therapeutic Approaches to Osteoarthritis", focuses on the molecular mechanisms of pathogenesis and therapeutic approaches to Osteoarthritis, which is a heterogeneous disease. We welcome papers on basic and translational research of Osteoarthritis.

Dr. Masato Sato
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.

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Keywords

  • mode of action
  • molecular mechanisms
  • pathogenesis
  • drug delivery
  • disease-modifying drug
  • translational research
  • cell therapy
  • regenerative medicine

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Published Papers (3 papers)

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Research

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16 pages, 8288 KiB  
Article
Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee
by Yasuyuki Sogo, Eriko Toyoda, Toshihiro Nagai, Takumi Takahashi, Daichi Takizawa, Masahiko Watanabe and Masato Sato
Int. J. Mol. Sci. 2024, 25(12), 6514; https://doi.org/10.3390/ijms25126514 - 13 Jun 2024
Viewed by 839
Abstract
Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and [...] Read more.
Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral–tibial (FT), femoral–patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn’s grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches to Osteoarthritis)
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14 pages, 2653 KiB  
Article
Osteophyte Cartilage as a Potential Source for Minced Cartilage Implantation: A Novel Approach for Articular Cartilage Repair in Osteoarthritis
by Shingo Kawabata, Tomoyuki Nakasa, Akinori Nekomoto, Dilimulati Yimiti, Shigeru Miyaki and Nobuo Adachi
Int. J. Mol. Sci. 2024, 25(10), 5563; https://doi.org/10.3390/ijms25105563 - 20 May 2024
Viewed by 1233
Abstract
Osteoarthritis (OA) is a common joint disorder characterized by cartilage degeneration, often leading to pain and functional impairment. Minced cartilage implantation (MCI) has emerged as a promising one-step alternative for large cartilage defects. However, the source of chondrocytes for MCI remains a challenge, [...] Read more.
Osteoarthritis (OA) is a common joint disorder characterized by cartilage degeneration, often leading to pain and functional impairment. Minced cartilage implantation (MCI) has emerged as a promising one-step alternative for large cartilage defects. However, the source of chondrocytes for MCI remains a challenge, particularly in advanced OA, as normal cartilage is scarce. We performed in vitro studies to evaluate the feasibility of MCI using osteophyte cartilage, which is present in patients with advanced OA. Osteophyte and articular cartilage samples were obtained from 22 patients who underwent total knee arthroplasty. Chondrocyte migration and proliferation were assessed using cartilage fragment/atelocollagen composites to compare the characteristics and regenerative potential of osteophytes and articular cartilage. Histological analysis revealed differences in cartilage composition between osteophytes and articular cartilage, with higher expression of type X collagen and increased chondrocyte proliferation in the osteophyte cartilage. Gene expression analysis identified distinct gene expression profiles between osteophytes and articular cartilage; the expression levels of COL2A1, ACAN, and SOX9 were not significantly different. Chondrocytes derived from osteophyte cartilage exhibit enhanced proliferation, and glycosaminoglycan production is increased in both osteophytes and articular cartilage. Osteophyte cartilage may serve as a viable alternative source of MCI for treating large cartilage defects in OA. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches to Osteoarthritis)
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Review

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18 pages, 973 KiB  
Review
Glycosphingolipids in Osteoarthritis and Cartilage-Regeneration Therapy: Mechanisms and Therapeutic Prospects Based on a Narrative Review of the Literature
by Kentaro Homan, Tomohiro Onodera, Masatake Matsuoka and Norimasa Iwasaki
Int. J. Mol. Sci. 2024, 25(9), 4890; https://doi.org/10.3390/ijms25094890 - 30 Apr 2024
Viewed by 1259
Abstract
Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the [...] Read more.
Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell-surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolisms and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Approaches to Osteoarthritis)
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