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Frontiers in Immunology 2023Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors.... (Review)
Review
Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors. Chronic deposition of monosodium urate (MSU) crystals in articular and periarticular spaces as well as subsequent activation of innate immune system in the condition of persistent hyperuricemia are the core mechanisms of GA. As is well known, drugs for GA therapy primarily consists of rapidly acting anti-inflammatory agents and life-long uric acid lowering agents, and their therapeutic outcomes are far from satisfactory. Although MSU crystals in articular cartilage detected by arthrosonography or in synovial fluid found by polarization microscopy are conclusive proofs for GA, the exact molecular mechanism of NLRP3 inflammasome activation in the course of GA still remains mysterious, severely restricting the early diagnosis and therapy of GA. On the one hand, the activation of Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome requires nuclear factor kappa B (NF-κB)-dependent transcriptional enhancement of NLRP3, precursor (pro)-caspase-1 and pro-IL-1β, as well as the assembly of NLRP3 inflammasome complex and sustained release of inflammatory mediators and cytokines such as IL-1β, IL-18 and caspase-1. On the other hand, NLRP3 inflammasome activated by MSU crystals is particularly relevant to the initiation and progression of GA, and thus may represent a prospective diagnostic biomarker and therapeutic target. As a result, pharmacological inhibition of the assembly and activation of NLRP3 inflammasome may also be a promising avenue for GA therapy. Herein, we first introduced the functional role of NLRP3 inflammasome activation and relevant biological mechanisms in GA based on currently available evidence. Then, we systematically reviewed therapeutic strategies for targeting NLRP3 by potentially effective agents such as natural products, novel compounds and noncoding RNAs (ncRNAs) in the treatment of MSU-induced GA mouse models. In conclusion, our present review may have significant implications for the pathogenesis, diagnosis and therapy of GA.
Topics: Humans; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Arthritis, Gouty; Inflammasomes; Polymorphism, Genetic; Genetic Predisposition to Disease; Cytokines
PubMed: 37051231
DOI: 10.3389/fimmu.2023.1137822 -
Osteoarthritis and Cartilage Oct 2022We conducted a systematic review in order to understand the relationship between imaging-visualised meniscus pathologies, hyaline cartilage, joint replacement and pain... (Review)
Review
OBJECTIVE
We conducted a systematic review in order to understand the relationship between imaging-visualised meniscus pathologies, hyaline cartilage, joint replacement and pain in knee osteoarthritis (OA).
DESIGN
A search of the Medline, Excerpta Medica database (EMBASE) and Cochrane library databases was performed for original publications reporting association between imaging-detected meniscal pathology (extrusion or tear/damage) and longitudinal and cross-sectional assessments of hyaline articular cartilage loss [assessed on magnetic resonance imaging (MRI)], incident joint replacement and pain (longitudinal and cross-sectional) in knee OA. Each association was qualitatively characterised by a synthesis of data from each analysis, based upon study design and quality scoring (including risk of bias assessment and adequacy of covariate adjustment using Cochrane recommended methodology).
RESULTS
In total 4,878 abstracts were screened and 82 publications were included (comprising 72 longitudinal analyses and 49 cross-sectional). Using high quality, well-adjusted data, meniscal extrusion and meniscal tear/damage were associated with longitudinal progression of cartilage loss, cross-sectional cartilage loss severity and joint replacement, independently of age, sex and body mass index (BMI). Medial and lateral meniscal tears were associated with cartilage loss when they occurred in the body and posterior horns, but not the anterior horns. There was a lack of high quality, well-adjusted meniscal pathology and pain publications and no clear independent association between meniscal extrusion or tear/damage with pain severity, progression in pain or incident frequent knee symptoms.
CONCLUSION
Meniscal features have strong associations with cartilage loss and joint replacement in knee OA, but weak associations with knee pain. Systematic review PROSPERO registration number: CRD 42020210910.
Topics: Arthroplasty, Replacement; Cartilage, Articular; Cross-Sectional Studies; Humans; Knee Joint; Magnetic Resonance Imaging; Menisci, Tibial; Osteoarthritis, Knee; Pain
PubMed: 35963512
DOI: 10.1016/j.joca.2022.08.002 -
Cell Communication and Signaling : CCS Apr 2023Osteoarthritis (OA) is a multifactorial chronic disease primarily characterized by the degeneration of articular cartilage. Currently, there is a lack of effective... (Review)
Review
Osteoarthritis (OA) is a multifactorial chronic disease primarily characterized by the degeneration of articular cartilage. Currently, there is a lack of effective treatments for OA other than surgery. The exploration of the mechanisms of occurrence is important in exploring other new and effective treatments for OA. The current evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays a vital role in cytogenesis and is involved in OA progression. The terms "JAK2", "STAT3", and "Osteoarthritis"were used in a comprehensive literature search in PubMed to further investigate the relationship between the JAK2/STAT3 signaling pathway and OA. This review focuses on the role and mechanism of JAK2/STAT3 signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation. In addition, this review summarizes recent evidence of therapeutic approaches to treat OA by targeting the JAK2/STAT3 pathway to accelerate the translation of evidence into the progression of strategies for OA treatment. Video abstract.
Topics: Humans; Chondrocytes; Janus Kinase 2; STAT3 Transcription Factor; Signal Transduction; Cartilage, Articular; Osteoarthritis
PubMed: 37013568
DOI: 10.1186/s12964-023-01094-4 -
Health Technology Assessment... Feb 2017The surfaces of the bones in the knee are covered with articular cartilage, a rubber-like substance that is very smooth, allowing frictionless movement in the joint and... (Review)
Review
BACKGROUND
The surfaces of the bones in the knee are covered with articular cartilage, a rubber-like substance that is very smooth, allowing frictionless movement in the joint and acting as a shock absorber. The cells that form the cartilage are called chondrocytes. Natural cartilage is called hyaline cartilage. Articular cartilage has very little capacity for self-repair, so damage may be permanent. Various methods have been used to try to repair cartilage. Autologous chondrocyte implantation (ACI) involves laboratory culture of cartilage-producing cells from the knee and then implanting them into the chondral defect.
OBJECTIVE
To assess the clinical effectiveness and cost-effectiveness of ACI in chondral defects in the knee, compared with microfracture (MF).
DATA SOURCES
A broad search was done in MEDLINE, EMBASE, The Cochrane Library, NHS Economic Evaluation Database and Web of Science, for studies published since the last Health Technology Assessment review.
REVIEW METHODS
Systematic review of recent reviews, trials, long-term observational studies and economic evaluations of the use of ACI and MF for repairing symptomatic articular cartilage defects of the knee. A new economic model was constructed. Submissions from two manufacturers and the ACTIVE (Autologous Chondrocyte Transplantation/Implantation Versus Existing Treatment) trial group were reviewed. Survival analysis was based on long-term observational studies.
RESULTS
Four randomised controlled trials (RCTs) published since the last appraisal provided evidence on the efficacy of ACI. The SUMMIT (Superiority of Matrix-induced autologous chondrocyte implant versus Microfracture for Treatment of symptomatic articular cartilage defects) trial compared matrix-applied chondrocyte implantation (MACI) against MF. The TIG/ACT/01/2000 (TIG/ACT) trial compared ACI with characterised chondrocytes against MF. The ACTIVE trial compared several forms of ACI against standard treatments, mainly MF. In the SUMMIT trial, improvements in knee injury and osteoarthritis outcome scores (KOOSs), and the proportion of responders, were greater in the MACI group than in the MF group. In the TIG/ACT trial there was improvement in the KOOS at 60 months, but no difference between ACI and MF overall. Patients with onset of symptoms < 3 years' duration did better with ACI. Results from ACTIVE have not yet been published. Survival analysis suggests that long-term results are better with ACI than with MF. Economic modelling suggested that ACI was cost-effective compared with MF across a range of scenarios.
LIMITATIONS
The main limitation is the lack of RCT data beyond 5 years of follow-up. A second is that the techniques of ACI are evolving, so long-term data come from trials using forms of ACI that are now superseded. In the modelling, we therefore assumed that durability of cartilage repair as seen in studies of older forms of ACI could be applied in modelling of newer forms. A third is that the high list prices of chondrocytes are reduced by confidential discounting. The main research needs are for longer-term follow-up and for trials of the next generation of ACI.
CONCLUSIONS
The evidence base for ACI has improved since the last appraisal by the National Institute for Health and Care Excellence. In most analyses, the incremental cost-effectiveness ratios for ACI compared with MF appear to be within a range usually considered acceptable. Research is needed into long-term results of new forms of ACI.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42014013083.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Cartilage Diseases; Chondrocytes; Cost-Benefit Analysis; Graft Survival; Humans; Knee Injuries; Knee Joint; Orthopedic Procedures; Osteoarthritis, Knee; State Medicine; United Kingdom
PubMed: 28244303
DOI: 10.3310/hta21060 -
Osteoarthritis and Cartilage Sep 2022The aim of this systematic review was to assess the effects of stem cell-based therapies on the treatment of Temporomandibular Joint Osteoarthritis (TMJ-OA) and the... (Review)
Review
OBJECTIVES
The aim of this systematic review was to assess the effects of stem cell-based therapies on the treatment of Temporomandibular Joint Osteoarthritis (TMJ-OA) and the regeneration of cartilage/osteochondral defects.
METHODS
Data on preclinical studies evaluating the effectiveness of stem cell-based therapies for treating Temporomandibular Disorders (TMDs) were extracted from PubMed, Web of Science, and Cochrane Library and the grey literature by three independent reviewers. A manual search was performed in the databases, the reference list of review studies, and relevant journals in the field. Compliance with the ARRIVE guidelines was evaluated for quality assessment. SYRCLE's risk of bias tool for animal experimental studies was assessed to define internal validity.
RESULTS
After applying the inclusion and exclusion criteria, 10 studies were included in the qualitative synthesis. Regardless of cell origin, stem cell-based therapeutic approaches induced protective, anti-inflammatory, and chondroregenerative potential in the treatment of TMJ-OA. Regeneration of the cartilage layer on the surface of the condyle was achieved when stem cells were directly flushed into the defect or when delivered within a carrier.
CONCLUSION
Stem cell-based therapies may be considered a promising approach for the treatment of TMJ-OA and for the regeneration of full-thickness cartilage and osteochondral defects in the TMJ. Human studies shall be performed to validate these results found in animals.
Topics: Animals; Cartilage, Articular; Humans; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Regeneration; Temporomandibular Joint
PubMed: 35597373
DOI: 10.1016/j.joca.2022.05.006 -
International Journal of Molecular... Jul 2021Temporomandibular joint osteoarthritis (TMJ OA) is a low-inflammatory disorder with multifactorial etiology. The aim of this review was to present the current state of...
Mechanisms of Action and Efficacy of Hyaluronic Acid, Corticosteroids and Platelet-Rich Plasma in the Treatment of Temporomandibular Joint Osteoarthritis-A Systematic Review.
Temporomandibular joint osteoarthritis (TMJ OA) is a low-inflammatory disorder with multifactorial etiology. The aim of this review was to present the current state of knowledge regarding the mechanisms of action and the efficacy of hyaluronic acid (HA), corticosteroids (CS) and platelet-rich plasma (PRP) in the treatment of TMJ OA.: The PubMed database was analyzed with the keywords: "(temporomandibular joint) AND ((osteoarthritis) OR (dysfunction) OR (disorders) OR (pain)) AND ((treatment) OR (arthrocentesis) OR (arthroscopy) OR (injection)) AND ((hyaluronic acid) OR (corticosteroid) OR (platelet rich plasma))". After screening of 363 results, 16 studies were included in this review. Arthrocentesis alone effectively reduces pain and improves jaw function in patients diagnosed with TMJ OA. Additional injections of HA, either low-molecular-weight (LMW) HA or high-molecular-weight (HMW) HA, or CS at the end of the arthrocentesis do not improve the final clinical outcomes. CS present several negative effects on the articular cartilage. Results related to additional PRP injections are not consistent and are rather questionable. Further studies should be multicenter, based on a larger group of patients and should answer the question of whether other methods of TMJ OA treatment are more beneficial for the patients than simple arthrocentesis.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis; Platelet-Rich Plasma; Signal Transduction; Temporomandibular Joint Disorders
PubMed: 34299024
DOI: 10.3390/ijms22147405 -
BMC Musculoskeletal Disorders Apr 2020Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of... (Meta-Analysis)
Meta-Analysis
Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis.
BACKGROUND
Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA.
METHODS
The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation.
RESULTS
Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: - 0.31; 95% confidence interval (CI): - 0.55 to - 0.06; P = 0.01 < 0.05). PRP combined with HA for KOA achieved better improvements in the WOMAC Function Score (SMD: -0.32; 95% CI: - 0.54 to - 0.10; P < 0.05) and WOMAC Total Score (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05) at the 12-month follow-up than did the application of PRP alone. In a comparison of Lequesne Index scores at the 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone (P > 0.05).
CONCLUSIONS
Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.
Topics: Combined Modality Therapy; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Knee; Pain Measurement; Platelet-Rich Plasma; Randomized Controlled Trials as Topic; Treatment Outcome; Viscosupplements
PubMed: 32278352
DOI: 10.1186/s12891-020-03262-w -
Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature.BMC Musculoskeletal Disorders Oct 2016Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to... (Review)
Review
BACKGROUND
Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease.
METHODS
The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies.
RESULTS
A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time.
CONCLUSIONS
This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population.
Topics: Cartilage, Articular; Chronic Pain; Disease Progression; Humans; Leg Bones; Metabolic Syndrome; Osteoarthritis, Knee; Qualitative Research; Risk Factors
PubMed: 27733199
DOI: 10.1186/s12891-016-1286-2 -
Osteoarthritis- a systematic review of long-term safety implications for osteoarthritis of the knee.BMC Musculoskeletal Disorders Apr 2019There is no cure for knee osteoarthritis (KOA) and typically patients live approximately 30-years with the disease. Most common medical treatments result in short-term...
BACKGROUND
There is no cure for knee osteoarthritis (KOA) and typically patients live approximately 30-years with the disease. Most common medical treatments result in short-term palliation of symptoms with little consideration of long-term risk. This systematic review aims to appraise the current evidence for the long-term (≥12 months) safety of common treatments for knee osteoarthritis (KOA).
METHODS
Cochrane Database of Systematic Reviews, Medline and PubMed were systematically searched from 1990 to July 2017, inclusive. Inclusion criteria were 1) peer-reviewed publications investigating treatments for KOA referred to in the Australian Clinical Care Standard and/or Therapeutic Guidelines: Rheumatology 2) specifically addressing safety of the treatments 3) with ≥12 months of follow-up and 4) Downs and Black quality score ≥ 13.
RESULTS
Thirty-four studies fulfilled the inclusion criteria. Lifestyle modifications (moderate exercise and weight loss), paracetamol, glucosamine, Intraarticular Hyaluronic Acid (IAHA) and platelet-rich-plasma (PRP) injections have a low risk of harm and beneficial ≥12 month outcomes. Although Nonsteroidal Anti-inflammatory Drugs (NSAIDs) provide pain relief, they are associated with increased risk of medical complications. Cortisone injections are associated with radiological cartilage degeneration at > 12 months. Arthroscopy for degenerative meniscal tears in KOA leads to a 3-fold increase in total knee arthroplasty (TKA). TKA improves primary outcomes of KOA but has a low rate of significant medical complications.
CONCLUSIONS
Given the safety and effectiveness of lifestyle interventions such as weight loss and exercise, these should be advocated in all patients due to the low risk of harm. The use of NSAIDs should be minimized to avoid gastrointestinal complications. Treatment with opioids has a lack of evidence for use and a high risk of long-term harm. The use of IAHA and PRP may provide additional symptomatic benefit without the risk of harm. TKA is associated with significant medical complications but is justified by the efficacy of joint replacement in late-stage disease.
TRIAL REGISTRATION
PROSPERO International prospective register for systematic reviews; registration number CRD42017072809 .
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Knee; Exercise Therapy; Humans; Injections, Intra-Articular; Osteoarthritis, Knee; Pain Management; Risk Reduction Behavior; Time Factors
PubMed: 30961569
DOI: 10.1186/s12891-019-2525-0 -
Osteoarthritis and Cartilage Jul 2018To determine the change in walking gait biomechanics after total hip arthroplasty (THA) for osteoarthritis (OA) compared to the pre-operative gait status, and to compare... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the change in walking gait biomechanics after total hip arthroplasty (THA) for osteoarthritis (OA) compared to the pre-operative gait status, and to compare the recovery of gait following THA with healthy individuals.
METHODS
Systematic review with meta-analysis of studies investigating changes in gait biomechanics after THA compared to (1) preoperative levels and (2) healthy individuals. Data were pooled at commonly reported time points and standardised mean differences (SMDs) were calculated in meta-analyses for spatiotemporal, kinematic and kinetic parameters.
RESULTS
Seventy-four studies with a total of 2,477 patients were included. At 6 weeks postoperative, increases were evident for walking speed (SMD: 0.32, 95% confidence intervals (CI) 0.14, 0.50), stride length (SMD: 0.40, 95% CI 0.19, 0.61), step length (SMD: 0.41, 95% CI 0.23, 0.59), and transverse plane hip range of motion (ROM) (SMD: 0.36, 95% CI 0.05, 0.67) compared to pre-operative gait. Sagittal, coronal and transverse hip ROM was significantly increased at 3 months (SMDs: 0.50 to 1.07). At 12 months postoperative, patients demonstrated deficits compared with healthy individuals for walking speed (SMD: -0.59, 95% CI -1.08 to -0.11), stride length (SMD: -1.27, 95% CI -1.63, -0.91), single limb support time (SMD: -0.82, 95% CI -1.23, -0.41) and sagittal plane hip ROM (SMD: -1.16, 95% CI -1.83, -0.49). Risk of bias scores ranged from seven to 24 out of 26.
CONCLUSIONS
Following THA for OA, early improvements were demonstrated for spatiotemporal and kinematic gait patterns compared to the pre-operative levels. Deficits were still observed in THA patients compared to healthy individuals at 12 months.
Topics: Aged; Arthroplasty, Replacement, Hip; Biomechanical Phenomena; Female; Gait; Humans; Male; Middle Aged; Osteoarthritis, Hip; Postoperative Period; Preoperative Period; Prognosis; Range of Motion, Articular; Recovery of Function; Severity of Illness Index; Time Factors; Walking Speed
PubMed: 29474993
DOI: 10.1016/j.joca.2018.02.897