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Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for...
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Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for Knee Osteoarthritis

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

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 20662

Special Issue Editor

Dr. Jai-Hong Cheng

E-Mail Website
Guest Editor
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
Interests: shockwave medicine; translational research; cell therapy; regeneration medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Knee osteoarthritis (OA) is a common disease caused by degeneration or trauma in joints that contributes to inflammation in the synovium, articular cartilage, and subchondral bone. Pathological changes are observed in knee OA, including synovitis, loss of extracellular matrix in the articular cartilage, chondrocyte death, tissue fibrosis, and cyst and osteophyte formation. Knee pain is a major symptom of OA that bothers people of all ages on a daily basis. There are also many other significant symptoms of knee OA, including swelling, stiffness, creaking joints, and difficulty in moving, which affect patients every day. The molecular mechanism of knee OA still needs to be explored further through clinical and preclinical studies. Determining how to identify, discover, and treat problems linked to knee OA are topics of concern and challenges for scientists around the world. Therefore, advances in molecular research in the pathology, prevention, diagnosis, and treatment of knee OA are within the scope of this Special Issue. Summaries of new findings, concepts, and molecular study directions in the form of review articles are also of interest in the Special Issue.

Dr. JaiHong Cheng
Guest Editor

Manuscript Submission Information

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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

  • knee osteoarthritis
  • signaling pathways
  • biomarkers
  • therapy
  • cytokines
  • growth factors
  • microRNA
  • proteomics
  • epigenomics
  • transcriptomics

Related Special Issue

Published Papers (7 papers)

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Research

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19 pages, 2384 KiB  
Article
Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment
by Giada Amodeo, Silvia Franchi, Giulia Galimberti, Laura Comi, Simona D’Agnelli, Marco Baciarello, Elena Giovanna Bignami and Paola Sacerdote
Biomedicines 2022, 10(11), 2847; https://doi.org/10.3390/biomedicines10112847 - 08 Nov 2022
Cited by 6 | Viewed by 2074
Abstract
Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may predispose to the development of frailty. Studies on mechanisms underlying pain in osteoarthritis models during aging are lacking. In this work, we used the monosodium iodoacetate model of [...] Read more.
Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may predispose to the development of frailty. Studies on mechanisms underlying pain in osteoarthritis models during aging are lacking. In this work, we used the monosodium iodoacetate model of osteoarthritis in adult (11-week-old) and old (20-month-old) C57BL/6J mice to compare hypersensitivity, locomotion, neuroinflammation, and the effects of morphine treatment. After osteoarthritis induction in adult and old mice, weight-bearing asymmetry, mechanical allodynia, and thermal hyperalgesia similarly developed, while locomotion and frailty were more affected in old than in adult animals. When behavioral deficits were present, the animals were treated for 7 days with morphine. This opioid counteracts the behavioral alterations and the frailty index worsening both in adult and old mice. To address the mechanisms that underlie pain, we evaluated neuroinflammatory markers and proinflammatory cytokine expression in the sciatic nerve, DRGs, and spinal cord. Overexpression of cytokines and glia markers were present in osteoarthritis adult and old mice, but the activation was qualitatively and quantitatively more evident in aged mice. Morphine was able to counteract neuroinflammation in both age groups. We demonstrate that old mice are more vulnerable to pain’s detrimental effects, but prompt treatment is successful at mitigating these effects. Full article
(This article belongs to the Special Issue Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for Knee Osteoarthritis)
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14 pages, 2631 KiB  
Article
Infiltration Profile of Regulatory T Cells in Osteoarthritis-Related Pain and Disability
by Timo Albert Nees, Jiji Alexander Zhang, Hadrian Platzer, Tilman Walker, Tobias Reiner, Elena Tripel, Babak Moradi and Nils Rosshirt
Biomedicines 2022, 10(9), 2111; https://doi.org/10.3390/biomedicines10092111 - 29 Aug 2022
Cited by 6 | Viewed by 1777
Abstract
Emerging evidence indicates that regulatory T cells (Treg) intervene in the inflammatory processes that drive osteoarthritis (OA). However, whether polarized Tregs affect clinical features of the disease in the short- or long-term, and if so, what their role in OA-related pain and functional [...] Read more.
Emerging evidence indicates that regulatory T cells (Treg) intervene in the inflammatory processes that drive osteoarthritis (OA). However, whether polarized Tregs affect clinical features of the disease in the short- or long-term, and if so, what their role in OA-related pain and functional disability really is, remains elusive. Thus, the aim of the current study was to characterize the infiltration profile of Tregs in systemic (peripheral blood) and joint-derived (synovial fluid and synovial membrane) samples from patients with knee OA in relation to OA-induced symptoms. To this end, Treg infiltration (CD4+CD25+/high CD127low/−) was analyzed in matched samples of peripheral blood (PB), synovial fluid (SF) and synovial membrane (SM) from a total of 47 patients undergoing elective knee arthroplasty using flow cytometry. At the same time, knee pain and function were assessed and correlated with Treg proportions in different compartments (PB, SF, SM). Interestingly, matched-pair analysis revealed significantly higher Treg proportions in joint-derived samples than in PB, which was mainly attributed to the high Treg frequency in SF. Moreover, we found significant associations between infiltrating Tregs and OA-related symptoms which indicate that lower Treg proportions—especially in the SM—are related to increased pain and functional disability in knee OA. In conclusion, this study highlights the importance of local cellular inflammatory processes in OA pathology. Intra-articular Treg infiltration might play an important role not only in OA pathogenesis but also in the development of OA-related symptoms. Full article
(This article belongs to the Special Issue Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for Knee Osteoarthritis)
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16 pages, 3461 KiB  
Article
Increased Chondroprotective Effect of Combining Hyaluronic Acid with a Glucocorticoid Compared to Separate Administration on Cytokine-Treated Osteoarthritic Chondrocytes in a 2D Culture
by Christoph Bauer, Lukas B. Moser, Vivek Jeyakumar, Eugenia Niculescu-Morzsa, Daniela Kern and Stefan Nehrer
Biomedicines 2022, 10(7), 1733; https://doi.org/10.3390/biomedicines10071733 - 18 Jul 2022
Cited by 3 | Viewed by 2085
Abstract
Intra-articular injections of glucocorticoids (GC) or hyaluronic acid (HA) are commonly used interventions for patients suffering from knee osteoarthritis (OA). Both substances are combined to achieve a chondroprotective and anti-inflammatory effect. Clinical studies have shown benefits, but data on the cellular level are [...] Read more.
Intra-articular injections of glucocorticoids (GC) or hyaluronic acid (HA) are commonly used interventions for patients suffering from knee osteoarthritis (OA). Both substances are combined to achieve a chondroprotective and anti-inflammatory effect. Clinical studies have shown benefits, but data on the cellular level are still lacking. This study aimed to investigate the effect of the GC triamcinolone hexacetonide, HA, and a mix of both substances on cytokine-treated chondrocytes in vitro. Chondrocytes isolated from human articular cartilage were seeded on 6- and 24-well plates. Mimicking OA’s inflammatory state, cells were treated with IL-1β and IL-17 for six days, whereby, after three days, test substances (10%) were added to the culture medium. Chondrocytes were analyzed on days three and six concerning their actin polymerization, expression of anabolic and catabolic genes, metabolic activity, cytokine release, and reactive oxygen species (ROS). Adding HA or GC/HA to the inflammatory culture medium increased the metabolic activity of chondrocytes, while groups containing GC reduced catabolic gene expression and the release of TNF-α. In addition, enhanced F-actin content was shown supplementing HA or GC/HA to the culture medium. Supplementing GC with HA leads to an anti-inflammatory and chondroprotective effect by diminishing the side effects of GC supplementation alone. Full article
(This article belongs to the Special Issue Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for Knee Osteoarthritis)
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14 pages, 7941 KiB  
Article
Lactobacillus acidophilus Mitigates Osteoarthritis-Associated Pain, Cartilage Disintegration and Gut Microbiota Dysbiosis in an Experimental Murine OA Model
by InSug O-Sullivan, Arivarasu Natarajan Anbazhagan, Gurjit Singh, Kaige Ma, Stefan J. Green, Megha Singhal, Jun Wang, Anoop Kumar, Pradeep K. Dudeja, Terry G. Unterman, Gina Votta-Velis, Benjamin Bruce, Andre J. van Wijnen and Hee-Jeong Im
Biomedicines 2022, 10(6), 1298; https://doi.org/10.3390/biomedicines10061298 - 01 Jun 2022
Cited by 17 | Viewed by 2681
Abstract
To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA by partial medial meniscectomy (PMM). Pain was assessed by von Frey filament and hot plate testing. Joint pathology and pain markers were comprehensively [...] Read more.
To test probiotic therapy for osteoarthritis (OA), we administered Lactobacillus acidophilus (LA) by oral gavage (2×/week) after induction of OA by partial medial meniscectomy (PMM). Pain was assessed by von Frey filament and hot plate testing. Joint pathology and pain markers were comprehensively analyzed in knee joints, spinal cords, dorsal root ganglia and distal colon by Safranin O/fast green staining, immunofluorescence microscopy and RT-qPCR. LA acutely reduced inflammatory knee joint pain and prevented further OA progression. The therapeutic efficacy of LA was supported by a significant reduction of cartilage-degrading enzymes, pain markers and inflammatory factors in the tissues we examined. This finding suggests a likely clinical effect of LA on OA. The effect of LA treatment on the fecal microbiome was assessed by 16S rRNA gene amplicon sequencing analysis. LA significantly altered the fecal microbiota compared to vehicle-treated mice (PERMANOVA p < 0.009). Our pre-clinical OA animal model revealed significant OA disease modifying effects of LA as reflected by rapid joint pain reduction, cartilage protection, and reversal of dysbiosis. Our findings suggest that LA treatment has beneficial systemic effects that can potentially be developed as a safe OA disease-modifying drug (OADMD). Full article
(This article belongs to the Special Issue Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for Knee Osteoarthritis)
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12 pages, 1989 KiB  
Article
Intra-Articular Injection of Platelet-Rich Plasma Is More Effective than Hyaluronic Acid or Steroid Injection in the Treatment of Mild to Moderate Knee Osteoarthritis: A Prospective, Randomized, Triple-Parallel Clinical Trial
by Dawid Szwedowski, Ali Mobasheri, Andrzej Moniuszko, Jan Zabrzyński and Sławomir Jeka
Biomedicines 2022, 10(5), 991; https://doi.org/10.3390/biomedicines10050991 - 25 Apr 2022
Cited by 7 | Viewed by 3411
Abstract
Purpose: To prospectively compare the efficacy and safety of intra-articular injections of platelet-rich plasma (PRP) with hyaluronic acid (HA) and glucocorticosteroid (CS) control groups for knee osteoarthritis (KOA) in a randomized, triple-parallel, single-center clinical trial. Methods: A total of 75 patients were randomly [...] Read more.
Purpose: To prospectively compare the efficacy and safety of intra-articular injections of platelet-rich plasma (PRP) with hyaluronic acid (HA) and glucocorticosteroid (CS) control groups for knee osteoarthritis (KOA) in a randomized, triple-parallel, single-center clinical trial. Methods: A total of 75 patients were randomly assigned to one of three groups receiving a single injection of either leukocyte-poor platelet-rich plasma (25 knees), hyaluronic acid (25 knees), or glucocorticosteroid (25 knees). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was collected at baseline and 6, 12, and 26 weeks after treatment. Results: After 6 weeks of PRP administration, a decrease in the mean WOMAC value was observed in all three study groups. Three months after administration, the greatest decrease in the mean WOMAC value was obtained in the PRP group. The results in the HA and CS groups were similar (p = 0.681). In the one-way analysis of variance and post hoc analysis using the HSD Tukey test, a significantly greater improvement was shown by comparing the PRP and CS groups (p = 0.001), and the PRP and HA groups (p = 0.010). After intra-articular injection of CS, the reduction in pain was greatest 6 weeks after administration, and the mean value was the lowest among all groups. During subsequent visits, the value of the pain subscale increased, and after 6 months, it was the highest among the studied groups. Using the Wilcoxon paired test, no PRP effect was found to reduce stiffness at the 6-month follow-up (p = 0.908). Functional improvement was achieved in all groups, i.e., a decrease in the value of this subscale 6 months after administration. The largest decrease was seen in the group that received PRP (p < 0.001) and then in the HA group. The smallest decrease among the investigated methods was shown in the CS group. Conclusions: Intra-articular injections of PRP can provide clinically significant functional improvement for at least 6 months in patients with mild to moderate KOA which is superior to HA or CS injections. Full article
(This article belongs to the Special Issue Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for Knee Osteoarthritis)
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14 pages, 10996 KiB  
Article
Intra-Articular Injections of Autologous Adipose Tissue or Platelet-Rich Plasma Comparably Improve Clinical and Functional Outcomes in Patients with Knee Osteoarthritis
by Jakub Kaszyński, Paweł Bąkowski, Bartosz Kiedrowski, Łukasz Stołowski, Anna Wasilewska-Burczyk, Kamilla Grzywacz and Tomasz Piontek
Biomedicines 2022, 10(3), 684; https://doi.org/10.3390/biomedicines10030684 - 16 Mar 2022
Cited by 11 | Viewed by 2656
Abstract
The use of biologic therapies for the management of knee osteoarthritis (OA) has largely increased in recent years. The purpose of this study was to evaluate the efficiency and the therapeutic potential of platelet-rich plasma (PRP) and autologous adipose tissue (AAT) injections as [...] Read more.
The use of biologic therapies for the management of knee osteoarthritis (OA) has largely increased in recent years. The purpose of this study was to evaluate the efficiency and the therapeutic potential of platelet-rich plasma (PRP) and autologous adipose tissue (AAT) injections as a treatment for knee OA. Sixty participants were enrolled in the study: 20 healthy ones and 40 with minimal to moderate knee OA (KL I-III). The OA patients were randomly assigned either to the PRP or to the AAT group. The PRP samples showed a low expression level of NF-κB-responsive gene CCL5 and high expression levels of classic inflammatory and TNF-l INF responses. The AAT injection product was prepared using a Lipogems device, and its regenerative potential as well as the ability for expansion of mesenchymal stem cells were tested in the cell culture conditions. The patient assessments were carried out five times. Significant improvement was observed regardless of the treatment method in the VAS, KOOS, WOMAC and IKDC 2000 subjective evaluations as well as in the functional parameters. Intra-articular injections of AAT or PRP improved pain, symptoms, quality of life and functional capacity with a comparable effectiveness in the patients with mild to moderate knee osteoarthritis. Full article
(This article belongs to the Special Issue Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for Knee Osteoarthritis)
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Review

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16 pages, 1342 KiB  
Review
The Corpus Adiposum Infrapatellare (Hoffa’s Fat Pad)—The Role of the Infrapatellar Fat Pad in Osteoarthritis Pathogenesis
by Sebastian Braun, Frank Zaucke, Marco Brenneis, Anna E. Rapp, Patrizia Pollinger, Rebecca Sohn, Zsuzsa Jenei-Lanzl and Andrea Meurer
Biomedicines 2022, 10(5), 1071; https://doi.org/10.3390/biomedicines10051071 - 05 May 2022
Cited by 9 | Viewed by 4907
Abstract
In recent years, the infrapatellar fat pad (IFP) has gained increasing research interest. The contribution of the IFP to the development and progression of knee osteoarthritis (OA) through extensive interactions with the synovium, articular cartilage, and subchondral bone is being considered. As part [...] Read more.
In recent years, the infrapatellar fat pad (IFP) has gained increasing research interest. The contribution of the IFP to the development and progression of knee osteoarthritis (OA) through extensive interactions with the synovium, articular cartilage, and subchondral bone is being considered. As part of the initiation process of OA, IFP secretes abundant pro-inflammatory mediators among many other factors. Today, the IFP is (partially) resected in most total knee arthroplasties (TKA) allowing better visualization during surgical procedures. Currently, there is no clear guideline providing evidence in favor of or against IFP resection. With increasing numbers of TKAs, there is a focus on preventing adverse postoperative outcomes. Therefore, anatomic features, role in the development of knee OA, and consequences of resecting versus preserving the IFP during TKA are reviewed in the following article. Full article
(This article belongs to the Special Issue Advanced Molecular Research on Pathology, Prevention, Diagnosis and Treatments for Knee Osteoarthritis)
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