Osteoarthritis Pathology and Treatment

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (27 October 2020) | Viewed by 23554

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Institute of Microbiology, 26 G. Bonchev Str. 1113 Sofia, Bulgaria
Interests: rheumatoid arthritis; osteoarthritis; candida albicans infections; complement system
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Dear Colleagues,

Among the over one hundred different types of arthritis conditions, osteoarthritis (OA) also known as degenerative arthritis is the most common, being a major cause of pain and disability in adult individuals. Our lack of full understanding of the basic mechanisms that initiate and sustain the disease remains a major obstacle in the search for an effective cure. The etiology of OA concerns joint injury, obesity, aging, and heredity. The investigations on the pathological processes of OA development are focused on OA symptoms, consisting of hypertrophy and apoptosis of articular chondrocytes, degradation of cartilage matrix, angiogenesis and calcification of hyaline cartilage, formation of osteophytes, degeneration of ligaments and remodeling of subchondral bone. The development of disease-modifying therapy for OA is embarrassed mainly because the onset and development of the disease involve complex molecular mechanisms. Most frequently, the disease is associated with pain complaints. The causes of pain appeared to be instability, increased pressure, hypertension and damage of sensitive structures like periosteum, ligaments and joint capsule. Among the multiple physiopathological mechanisms involved in OA, in particular those concerning sex hormone control such as estrogens have been attracting much attention. Recent direction in osteoimmunology is devoted to the signaling pathway(s) controlling the pathological processes in OA. New approaches for blocking the mechanisms involved in synovial inflammation, degeneration of articular cartilage, and subchondral bone remodeling can lead to targeted therapy for OA.

Prof. Nina Ivanovska
Guest Editor

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Keywords

  • disease-modifying therapies
  • genetic factors
  • mediators of OA
  • obesity and aging
  • osteophyte formation and pain
  • remodeling markers
  • role of estrogens
  • signaling pathways

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Related Special Issue

Published Papers (6 papers)

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Research

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13 pages, 8354 KiB  
Article
Treadmill Exercise after Controlled Abnormal Joint Movement Inhibits Cartilage Degeneration and Synovitis
by Yuichiro Oka, Kenij Murata, Kaichi Ozone, Takuma Kano, Yuki Minegishi, Aya Kuro-Nakajima, Kohei Arakawa, Takanori Kokubun and Naohiko Kanemura
Life 2021, 11(4), 303; https://doi.org/10.3390/life11040303 - 1 Apr 2021
Cited by 6 | Viewed by 2436
Abstract
Cartilage degeneration is the main pathological component of knee osteoarthritis (OA), but no effective treatment for its control exists. Although exercise can inhibit OA, the abnormal joint movement with knee OA must be managed to perform exercise. Our aims were to determine how [...] Read more.
Cartilage degeneration is the main pathological component of knee osteoarthritis (OA), but no effective treatment for its control exists. Although exercise can inhibit OA, the abnormal joint movement with knee OA must be managed to perform exercise. Our aims were to determine how controlling abnormal joint movement and treadmill exercise can suppress cartilage degeneration, to analyze the tissues surrounding articular cartilage, and to clarify the effect of treatment. Twelve-week-old ICR mice (n = 24) underwent anterior cruciate ligament transection (ACL-T) surgery on their right knees and were divided into three groups as follows: ACL-T, animals in the walking group subjected to ACL-T; controlled abnormal joint movement (CAJM), and CAJM with exercise (CAJM + Ex) (n = 8/group). Walking-group animals were subjected to treadmill exercise 6 weeks after surgery, including walking for 18 m/min, 30 min/day, 3 days/week for 8 weeks. Safranin-O staining, hematoxylin-eosin staining, and immunohistochemical staining were performed. The OARSI (Osteoarthritis research Society international) score was lower in the CAJM group than in the ACL-T group and was even lower in the CAJM + Ex group. The CAJM group had a lower meniscal injury score than the ACL-T group, and the CAJM + Ex group demonstrated a less severe synovitis than the ACL-T and CAJM groups. The observed difference in the perichondrium tissue damage score depending on the intervention method suggests different therapeutic effects, that normalizing joint motion can solve local problems in the knee joint, and that the anti-inflammatory effect of treadmill exercise can suppress cartilage degeneration. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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14 pages, 3448 KiB  
Article
Systematic Postoperative Assessment of a Minimally-Invasive Sheep Model for the Treatment of Osteochondral Defects
by Long Xin, Joerg Mika, Victoria Horbert, Sabine Bischoff, Harald Schubert, Juliane Borowski, Stefan Maenz, René Huber, Andre Sachse, Bernhard Illerhaus and Raimund W. Kinne
Life 2020, 10(12), 332; https://doi.org/10.3390/life10120332 - 7 Dec 2020
Cited by 1 | Viewed by 2432
Abstract
To assess the clinical course of a sheep stifle joint model for osteochondral (OC) defects, medial femoral condyles (MFC) were exposed without patella luxation using medial parapatellar skin (3–4 cm) and deep incisions (2–3 cm). Two defects (7 mm diameter; 10 mm depth; [...] Read more.
To assess the clinical course of a sheep stifle joint model for osteochondral (OC) defects, medial femoral condyles (MFC) were exposed without patella luxation using medial parapatellar skin (3–4 cm) and deep incisions (2–3 cm). Two defects (7 mm diameter; 10 mm depth; OC punch) were left empty or refilled with osteochondral autologous transplantation cylinders (OATS) and explanted after six weeks. Incision-to-suture time, anesthesia time, and postoperative wound or impairment scores were compared to those in sham-operated animals. Implant performance was assessed by X-ray, micro-computed tomography, histology, and immunohistology (collagens 1, 2; aggrecan). There were no surgery-related infections or patellar luxations. Operation, anesthesia, and time to complete stand were short (0.5, 1.4, and 1.5 h, respectively). The wound trauma score was low (0.4 of maximally 4; day 7). Empty-defect and OATS animals reached an impairment score of 0 significantly later than sham animals (7.4 and 4.0 days, respectively, versus 1.5 days). Empty defects showed incomplete healing and dedifferentiation/heterotopic differentiation; OATS-filled defects displayed advanced bone healing with remaining cartilage gaps and orthotopic expression of bone and cartilage markers. Minimally-invasive, medial parapatellar surgery of OC defects on the sheep MFC allows rapid and low-trauma recovery and appears well-suited for implant testing. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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14 pages, 1122 KiB  
Article
Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery
by Elena V. Tchetina, Kseniya E. Glemba, Galina A. Markova, Evgeniy A. Naryshkin, Elena A. Taskina, Maksim A. Makarov and Aleksandr M. Lila
Life 2020, 10(10), 224; https://doi.org/10.3390/life10100224 - 30 Sep 2020
Cited by 11 | Viewed by 3377
Abstract
Osteoarthritis (OA) pain implies an indication for joint replacement in patients with end-stage OA. However, chronic postoperative pain is observed in 10–40% of patients with OA. Here, we identified genes whose expression in the peripheral blood before surgery could denote the risk of [...] Read more.
Osteoarthritis (OA) pain implies an indication for joint replacement in patients with end-stage OA. However, chronic postoperative pain is observed in 10–40% of patients with OA. Here, we identified genes whose expression in the peripheral blood before surgery could denote the risk of postoperative pain development. We examined the peripheral blood of 26 healthy subjects and 50 patients with end-stage OA prior to joint replacement surgery. Pain was evaluated before surgery using the visual analog scale (VAS) index and neuropathic pain questionnaires, Douleur Neuropathique 4 Questions (DN4) and PainDETECT questionnaires. Functional activity was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Three and six months after surgery, pain indices according to VAS of 30% and higher were considered. Metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)1 protein levels were measured using ELISA in the peripheral blood mononuclear cells (PBMCs). Total RNA isolated from whole blood was analysed using quantitative real-time RT-PCR for caspase-3, MMP-9, TIMP1, cathepsins K and S, tumour necrosis factor (TNF)α, interleukin (IL)-1β, and cyclooxygenase (COX)-2 gene expression. Seventeen patients reported post-surgical pain. Expression of cathepsins K and S, caspase-3, TIMP1, IL-1β, and TNFα genes before surgery was significantly higher in these patients compared to pain-free patients with OA. Receiver-operating characteristic (ROC) curve analyses confirmed significant associations between these gene expressions and the likelihood of pain development after arthroplasty. High baseline expression of genes associated with extracellular matrix destruction (cathepsins S and K, TIMP1), inflammation (IL-1β, TNFα), and apoptosis (caspase-3) measured in the peripheral blood of patients with end-stage OA before knee arthroplasty might serve as an important biomarker of postoperative pain development. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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12 pages, 2262 KiB  
Article
Discovery of N-glycan Biomarkers for the Canine Osteoarthritis
by Hyunjun Lee, Ahyun Lee, Nari Seo, Jiwon Oh, Oh-Kyeong Kweon, Hyun Joo An and Jaehan Kim
Life 2020, 10(9), 199; https://doi.org/10.3390/life10090199 - 14 Sep 2020
Cited by 4 | Viewed by 2971
Abstract
Protein glycosylation is a post-translational modification that impacts on protein activity, stability, and interactions. It was sensitively altered by the cellular state and, therefore, is now used for a diagnostic or prognostic indicator of various human diseases such as cancer. To evaluate the [...] Read more.
Protein glycosylation is a post-translational modification that impacts on protein activity, stability, and interactions. It was sensitively altered by the cellular state and, therefore, is now used for a diagnostic or prognostic indicator of various human diseases such as cancer. To evaluate the clinical feasibility in the veterinary area, the N-glycan biomarkers were discovered from canine serum for the diagnosis of osteoarthritis (OA), which is one of the most common diseases of dogs. N-glycome was obtained from 20 μL of canine serum by the enzymatic cleavage followed by the purification and enrichment using solid-phase extraction. Independent compositions of 163 and 463 N-glycans were found from healthy control (n = 41) and osteoarthritis patients (n = 92), respectively. Initially, 31 of the potential biomarkers were screened by the p-values below 1.0 × 10−10 from ANOVA. Then, the area under the curve (AUC) and the intensity ratio between OA patient and healthy control (P/C ratio) were calculated. Considering the diagnostic efficacy, the AUC bigger than 0.9 and the P/C ratio larger than 3.0 were used to discover 16 N-glycans as diagnostic biomarkers. Particularly, five of the diagnostic biomarkers were AUC above 0.99 and three of N-glycans had AUC 1.0. The results suggest a clear possibility for N-glycan biomarkers to be used as a clinical tool in the veterinary medical area enabling to provide objective and non-invasive diagnostic information. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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Review

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13 pages, 974 KiB  
Review
The Role of Fibrosis in Osteoarthritis Progression
by Yeri Alice Rim and Ji Hyeon Ju
Life 2021, 11(1), 3; https://doi.org/10.3390/life11010003 - 23 Dec 2020
Cited by 68 | Viewed by 7686
Abstract
Osteoarthritis (OA) is a chronic degenerative joint disease where the main characteristics include cartilage degeneration and synovial membrane inflammation. These changes in the knee joint eventually dampen the function of the joint and restrict joint movement, which eventually leads to a stage where [...] Read more.
Osteoarthritis (OA) is a chronic degenerative joint disease where the main characteristics include cartilage degeneration and synovial membrane inflammation. These changes in the knee joint eventually dampen the function of the joint and restrict joint movement, which eventually leads to a stage where total joint replacement is the only treatment option. While much is still unknown about the pathogenesis and progression mechanism of OA, joint fibrosis can be a critical issue for better understanding this disease. Synovial fibrosis and the generation of fibrocartilage are the two main fibrosis-related characteristics that can be found in OA. However, these two processes remain mostly misunderstood. In this review, we focus on the fibrosis process in OA, especially in the cartilage and the synovium tissue, which are the main tissues involved in OA. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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Other

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13 pages, 1725 KiB  
Brief Report
Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis
by Ravindra Kolhe, Virgenal Owens, Ashok Sharma, Tae Jin Lee, Wenbo Zhi, Umar Ghilzai, Ashis K. Mondal, Yutao Liu, Carlos M. Isales, Mark W. Hamrick, Monte Hunter and Sadanand Fulzele
Life 2020, 10(12), 337; https://doi.org/10.3390/life10120337 - 10 Dec 2020
Cited by 25 | Viewed by 3801
Abstract
Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of [...] Read more.
Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling. Molecular profiling of the synovial fluid-derived EVs cargo in women may help in the discovery of novel biomarkers and therapeutics for the treatment of OA in women. Previously, we reported that synovial fluid-derived EV miRNA cargo differs in a sex-specific manner. This study aims to characterize synovial fluid-derived EV protein cargo in OA patients. Our data showed sex-specific EVs protein content in OA. We found haptoglobin, orosomucoid, and ceruloplasmin significantly up-regulated, whereas apolipoprotein down-regulated in female OA EVs. In males, we discovered β-2-glycoprotein, and complement component 5 proteins significantly up-regulated and Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 down-regulated in male OA EVs. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analysis revealed OA-specific protein involvement in several biological, molecular, and cellular pathways, specifically in inflammatory processes. In conclusion, synovial fluid EV protein content is altered in a sex-specific manner with OA, explaining the increased prevalence and severity of OA in women. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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