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Biomedicines
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Osteoarthritis: Molecular Pathways and Novel Therapeutic Strategies
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Osteoarthritis: Molecular Pathways and Novel Therapeutic Strategies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: closed (20 December 2024) | Viewed by 4887

Special Issue Editors

Dr. Antonia Patruno

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Guest Editor
Department of Medicine and Aging Science, University “G. D’Annunzio” Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
Interests: oxidative/nitrosative stress; cell signalling; tissue repair; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Teresa Paolucci

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Guest Editor
Department of Oral, Medical and Biotechnological Sciences, Physical Medicine and Rehabilitation, University G. D’Annunzio, Via dei Vestini, 31, 66100 Chieti, Italy
Interests: rehabilitation; pain; posture and balance; exercise; breast cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Mirko Pesce

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Guest Editor
Department of Medicine and Ageing Sciences University G. d’Annunzio, Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
Interests: autophagy; apoptosis; myokines; oxidative stress; inflammation; aging
Special Issues, Collections and Topics in MDPI journals
Dr. Andrea Pantalone

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Guest Editor
Orthopaedic and Traumatology Unit, Department of Medicine and Science of Aging, University G. "d'Annunzio" of Chieti-Pescara, Chieti, Italy
Interests: osteoarthritis; cartilage biology; orthopedic research; regenerative medicine; sports

Special Issue Information

Dear Colleagues,

Osteoarthritis (OA) is a prevalent and degenerative joint disorder characterized by the progressive deterioration of joint cartilage and the surrounding structures. It is the most common form of arthritis and often affects weight-bearing joints such as the knees, hips. Osteoarthritis (OA) exhibits a spectrum of clinical phenotypes, reflecting the heterogeneous nature of this prevalent joint disorder: (1) Chronic Pain Phenotype (Emphasizes central mechanisms, such as central sensitization; Characterized by persistent pain, potentially influencing treatment strategies); (2) Inflammatory Phenotype (Marked by elevated levels of inflammatory biomarkers); (3) Metabolic Syndrome Phenotype (Exhibits a high prevalence of obesity, diabetes, and metabolic disturbances); (4) Bone and Cartilage Metabolism Phenotype (Involves alterations in local tissue metabolism); (5) Mechanical Overload Phenotype (Primarily characterized by varus malalignment and medial compartment disease); (6) Minimal Joint Disease Phenotype (Characterized by minor clinical symptoms with slow progression). These distinct phenotypes, characterized by varying patterns of symptoms, disease progression, and treatment responses, play a pivotal role in tailoring effective interventions for individuals affected by OA. Recognizing and categorizing individuals based on these phenotypes holds promise for refining therapeutic strategies and improving overall outcomes in the diverse landscape of osteoarthritis. This Special Issue, will include a selection of original articles and reviews aimed at expanding our awareness and new insights into molecular and cellular mechanisms, key signaling pathways and novel therapeutic strategies in the treatment of osteoarthritis disease.

Dr. Antonia Patruno
Dr. Teresa Paolucci
Dr. Mirko Pesce
Dr. Andrea Pantalone
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. Biomedicines 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 2600 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
  • cartilage
  • pain
  • orthopedics
  • rehabilitation

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Published Papers (5 papers)

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Research

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15 pages, 2012 KiB  
Article
Long-Term Efficacy of Carboxymethyl-Chitosan in Advanced Knee Osteoarthritis: A Twelve-Month Follow-Up Study on Non-Responders to Hyaluronic Acid
by Nicola Manocchio, Carmelo Pirri, Concetta Ljoka, Andrea Sorbino, Nicolò Piacentini, Cristiano Monello, Giulia Vita and Calogero Foti
Biomedicines 2025, 13(2), 270; https://doi.org/10.3390/biomedicines13020270 - 22 Jan 2025
Viewed by 597
Abstract
Background: Knee osteoarthritis (OA) is a prevalent degenerative joint disease characterized by the degeneration of joint cartilage. Knee OA leads to pain, stiffness, swelling, and decreased mobility, significantly impacting the quality of life of affected people. Advanced-stage osteoarthritis often necessitates surgical intervention [...] Read more.
Background: Knee osteoarthritis (OA) is a prevalent degenerative joint disease characterized by the degeneration of joint cartilage. Knee OA leads to pain, stiffness, swelling, and decreased mobility, significantly impacting the quality of life of affected people. Advanced-stage osteoarthritis often necessitates surgical intervention due to poor response to conventional treatments, such as intra-articular hyaluronic acid (HA). Carboxymethyl-chitosan (CM-C), an emerging therapeutic agent, has shown potential in reducing inflammation, improving lubrication, and enhancing joint function. This study aimed to evaluate the long-term efficacy of CM-C injections in patients with advanced knee osteoarthritis, non-responders to HA. Methods: This retrospective study included 16 patients (mean age: 79.56 years) with Kellgren–Lawrence grade 3–4 knee OA treated with a single intra-articular injection of CM-C. Pain and functional outcomes were assessed using the Visual Analogue Scale (VAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline (T0), one month (T1), three months (T2), six months (T3), and twelve months (T4). Results: Significant pain reduction was observed at early follow up, (VAS: T1 p = 0.0002, T2 p = 0.0265; KOOS Pain: T1 p = 0.0014). However, pain partially returned by T3 and T4. KOOS activities of daily living (p = 0.0005), QoL (p = 0.0396), and Sport and Free Time (p = 0.0367) subscales showed significant improvement at T1, though worsening trends were observed in subsequent follow up with raw values suggesting persistent benefits. Strong negative correlations were found between VAS and KOOS subscales at various follow ups. Conclusions: A single CM-C injection demonstrated early pain relief and functional improvement in advanced knee OA for non-responders to HA. However, the long-term effects may diminish over time, necessitating a careful consideration of re-treatment strategies or combined therapies. Full article
(This article belongs to the Special Issue Osteoarthritis: Molecular Pathways and Novel Therapeutic Strategies)
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12 pages, 7537 KiB  
Article
Comparison of Biocompatibility of 3D-Printed Ceramic and Titanium in Micropig Ankle Hemiarthroplasty
by Si-Wook Lee, Donghyun Lee, Junsik Kim, Sanghyun An, Chul-Hyun Park, Jung-Min Lee, Chang-Jin Yon and Yu-Ran Heo
Biomedicines 2024, 12(12), 2696; https://doi.org/10.3390/biomedicines12122696 - 26 Nov 2024
Viewed by 600
Abstract
Background: Ankle arthritis is a common degenerative disease that progresses as cartilage damage in the lower tibia and upper talus progresses, resulting in loss of joint function. In addition to typical arthritis, there is also structural bone loss in the talus due to [...] Read more.
Background: Ankle arthritis is a common degenerative disease that progresses as cartilage damage in the lower tibia and upper talus progresses, resulting in loss of joint function. In addition to typical arthritis, there is also structural bone loss in the talus due to diseases such as talar avascular necrosis. Total talus replacement surgery is the procedure of choice in end-stage ankle arthritis and consists of a tibial, talar component and an insert. However, in cases of severe cartilage and bone damage to the talar bone with less damage to the tibial cartilage, a talar component hemiarthroplasty may be considered. Although the application of total talus replacement surgery using ceramics has been studied, reports on the application of metal 3D printing technology are limited. We aimed to investigate the feasibility of partial talar components using ceramic and titanium 3D printing technology in terms of biocompatibility and stability through animal experiments. Methods: Preoperative 3D CT was acquired and converted to STL files to fabricate a partial talus component for ankle hemiarthroplasty using ceramic and titanium. Six minipigs with an average age of 17 months were implanted with three ceramic (C-group) and three titanium talar components (T-group) in the hind limb ankle joint. The surgery was performed under anesthesia in a sterile operating room and was performed by two experienced foot and ankle specialist orthopedic surgeons. Blood analysis and CT were performed before surgery and every month for 3 months after surgery to assess the extent of inflammatory response and physical stability, sacrifices were performed 3 months after surgery, and H&E staining and micro-CT analysis were performed to compare histological biocompatibility. A grading score was calculated to semi-quantitative assess and compare the two groups. Results: In the postsurgical evaluation, blood analysis revealed that both groups had increased white blood cell counts on the postoperative day after surgery. The white blood cell count increased more in the titanium group (1.85-fold) than in the ceramic group (1.45-fold). After 3 months, all values normalized. During the study, CT analysis confirmed that all artificial samples were displaced from their initial positions. In micro-CT analysis, the adhesive tissue score of the ceramic artificial sample was better than that of the titanium sample (average threshold = 3027.18 ± 405.92). In histologic and grading scores for the inflammatory reactions, the average inflammation indices of the ceramic and titanium groups were 2.0 and 1.21, respectively. Also, the average grade score confirmed based on the results of fibrous tissue proliferation and new blood vessels was 18.4 in the ceramic application group and 12.3 in the titanium application group. Conclusions: In conclusion, both titanium and ceramics have excellent biocompatibility for artificial joints, and ceramic materials can be used as novel artificial joints. Further research on the strength and availability of these ceramics is required. Full article
(This article belongs to the Special Issue Osteoarthritis: Molecular Pathways and Novel Therapeutic Strategies)
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10 pages, 433 KiB  
Article
Evaluating Synergistic Effects of Hyaluronic Acid, Human Umbilical Cord-Derived Mesenchymal Stem Cells, and Growth Hormones in Knee Osteoarthritis: A Multi-Arm Randomized Trial
by Ismail Hadisoebroto Dilogo, Anissa Feby Canintika, Bernadus Riyan Hartanto, Jacub Pandelaki and Irsa Gagah Himantoko
Biomedicines 2024, 12(10), 2332; https://doi.org/10.3390/biomedicines12102332 - 14 Oct 2024
Viewed by 1330
Abstract
Background: Knee osteoarthritis (OA) significantly affects quality of life and imposes economic burdens due to its prevalence and the disability it causes. The efficacy of current treatments is limited to alleviating the symptoms, and they cannot be used for regenerative purposes. This study [...] Read more.
Background: Knee osteoarthritis (OA) significantly affects quality of life and imposes economic burdens due to its prevalence and the disability it causes. The efficacy of current treatments is limited to alleviating the symptoms, and they cannot be used for regenerative purposes. This study aims to evaluate the efficacy and safety of combining hyaluronic acid (HA), human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), and synthetic human growth hormone (somatotropin) in the treatment of knee OA, assessing pain relief, functional improvement, and cartilage regeneration. Methods: A four-arm, double-blind randomized trial was conducted with 51 knees from 28 subjects aged ≥50 with primary knee OA. The treatments involved were HA alone, HA with hUC-MSCs, HA with somatotropin, and a combination of all three. Efficacy was measured through the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and visual analog score (VAS), and MRI T2 mapping of cartilage was conducted on pre-implantation at the 6th and 12th month. Results: All treatment arms showed improvements in the VAS and WOMAC scores over 12 months, suggesting some pain relief and functional improvement. However, MRI T2 mapping showed no significant cartilage regeneration across the groups. Conclusions: While the combined use of HA, hUC-MSCs, and somatotropin improved symptoms of knee OA, it did not enhance cartilage regeneration significantly. This study highlights the potential of these combinations for symptom management but underscores the need for further research to optimize these therapies for regenerative outcomes. Full article
(This article belongs to the Special Issue Osteoarthritis: Molecular Pathways and Novel Therapeutic Strategies)
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Review

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20 pages, 691 KiB  
Review
Advances and Challenges in the Pursuit of Disease-Modifying Osteoarthritis Drugs: A Review of 2010–2024 Clinical Trials
by Mckenzie D. Brandt, Jason B. Malone and Thomas J. Kean
Biomedicines 2025, 13(2), 355; https://doi.org/10.3390/biomedicines13020355 - 4 Feb 2025
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Abstract
Background/Objectives: Osteoarthritis (OA) is a highly prevalent, degenerative joint disease capable of causing severe pain and impaired mobility. Current treatments mitigate symptoms but do not cure the disease. The development of a disease-modifying osteoarthritis drug (DMOAD) could improve patient outcomes by slowing, [...] Read more.
Background/Objectives: Osteoarthritis (OA) is a highly prevalent, degenerative joint disease capable of causing severe pain and impaired mobility. Current treatments mitigate symptoms but do not cure the disease. The development of a disease-modifying osteoarthritis drug (DMOAD) could improve patient outcomes by slowing, halting, or reversing joint damage. Many DMOADs have progressed to clinical trials, but very few have made a significant impact, and none have been approved for clinical use. The purpose of this review is to present an update on the current status of DMOADs with a particular focus on results published since 2010. Methods: A comprehensive search was conducted within PubMed and ClinicalTrials.gov for novel DMOADs enrolled in phase II and III clinical trials between 1 January 2010 and 1 July 2024. Results: Eleven DMOAD candidates are reviewed and critically analyzed for their potential benefit in OA treatment—Lorecivivint (SM04690), TissueGene-C, Cindunistat (SD-6010), Sprifermin, UBX0101, TPX-100, GLPG1972/S201086, Lutikizumab (ABT-981), SAR113945, MIV-711, and LNA043—and relevant challenges to their development are discussed. Conclusions: Six DMOADs have demonstrated statistically significant evidence of a structural or symptomatic benefit without major safety concerns in phase II and III randomized controlled trials post-2010. Full article
(This article belongs to the Special Issue Osteoarthritis: Molecular Pathways and Novel Therapeutic Strategies)
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17 pages, 1195 KiB  
Review
Comparative Analysis of Osteoarthritis Therapeutics: A Justification for Harnessing Retrospective Strategies via an Inverted Pyramid Model Approach
by Quinn T. Ehlen, Jacob Jahn, Ryan C. Rizk and Thomas M. Best
Biomedicines 2024, 12(11), 2469; https://doi.org/10.3390/biomedicines12112469 - 28 Oct 2024
Viewed by 1174
Abstract
In this review, we seek to explore two distinct approaches to the clinical management of OA: a prospective approach, addressing primarily one’s genetic predisposition to OA and generating early intervention options, and the retrospective approach, aimed at halting or reversing OA progression post-symptom [...] Read more.
In this review, we seek to explore two distinct approaches to the clinical management of OA: a prospective approach, addressing primarily one’s genetic predisposition to OA and generating early intervention options, and the retrospective approach, aimed at halting or reversing OA progression post-symptom onset. The clinical management of OA remains challenging, largely due to the limited availability of preventative treatments and failure of existing therapies to modify or reverse the underlying pathophysiology. The prospective approach involves the identification of genetic markers associated with OA and utilizes in vitro and in vivo models to characterize the underlying disease mechanism. Further, this approach focuses on identifying genetic predispositions and unique molecular subtypes of OA to develop individualized treatment plans based on patient genotypes. While the current literature investigating this strategy has been notable, this approach faces substantial challenges, such as extensive time burdens and utilization of extensive genetic testing that may not be economically feasible. Additionally, there is questionable justification for such extensive investigations, given OA’s relatively low mortality rates and burden when contrasted with diseases like specific forms of cancer, which rely heavily on the prospective approach. Alternatively, the retrospective approach primarily focuses on intervention following symptom onset and aims to utilize novel therapeutics to slow or reverse the inflammatory cascade typically seen in disease progression. These treatments, like Hippo pathway inhibitors, have shown initial promise in halting OA progression and alleviating OA symptomology by modulating cellular processes to preserve articular cartilage. In comparison to the prospective approach, the retrospective strategy is likely more cost-effective, more widely applicable, and does not necessitate thorough and invasive genetic screening. However, this approach must still be weighed against the typical natural history of disease progression, which frequently results in total knee arthroplasty and unacceptable outcomes for 15–20% of patients. From a comparative analysis of these two approaches, this review argues that the retrospective strategy, with ideally lower time and economic burden and greater accessibility, offers a more reasonable and effective solution in the context of OA management. Using a similar approach to other management of chronic diseases, we suggest an “Inverted Pyramid” model algorithm, a structured research and development regimen that prioritizes generating widely effective therapies first, with subsequent refinement of treatments based on the development of patient resistance to these therapies. We argue that this strategy may reduce the need for total knee arthroplasty while improving patient outcomes and accessibility. Full article
(This article belongs to the Special Issue Osteoarthritis: Molecular Pathways and Novel Therapeutic Strategies)
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