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1.
Bull Hosp Jt Dis (2013) ; 82(1): 91-99, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38431983

RESUMO

Osteochondral lesions (OCL) of the knee are a common pathology that can be challenging to address. Due to the innate characteristics of articular cartilage, OCLs generally do not heal in adults and often progress to involve the subchondral bone, ultimately resulting in the development of osteoarthritis. The goal of articular cartilage repair is to provide a long-lasting repair that replicates the biological and mechanical properties of articular cartilage, but there is no widely adopted technique that results in true pre-injury state hyaline cartilage. Current treatment modalities have seen reasonable clinical success, but significant limitations remain. Microfracture provides short-term benefit with a fibrocartilage-based repair. While osteochondral autograft or allograft and autologous chondrocyte implantation can be effective, each have their strengths and shortcomings. Emerging concepts in cartilage repair, including scaffold engineering and one stage cell-based options, are continually advancing. These have the benefits of reduced surgical morbidity and potentially improved integration with surrounding articular cartilage but have not yet reached widespread clinical application. Tissue engineering strategies and gene therapy have the potential to advance the field, however, they remain in the early stages. The current article reviews the structure and physiology of articular cartilage, the strengths and limitations of present treatment modalities, and the newer ongoing innovations that may change the way we approach osteochondral lesions and osteoarthritis.


Assuntos
Cartilagem Articular , Procedimentos Ortopédicos , Osteoartrite , Adulto , Humanos , Cartilagem Articular/cirurgia , Articulação do Joelho
2.
J Bodyw Mov Ther ; 37: 90-93, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38432847

RESUMO

BACKGROUND: Retinacula of the ankle are thickening of the deep fascia of the leg (crural fascia) and foot i.e. inseparable structures. Recent studies report their crucial role in functional stability and proprioception of the ankle. CASE PRESENTATION: A 38-yr-old Caucasian man - with a history of lateral malleolus fracture 12 years ago, obesity and right ankle osteoarthritis - was referred to a physiatrist for a right ankle pain that had significantly worsened over the last year. During walking, the patient experienced stinging pain in the area of tibialis anterior and peroneus tertius muscles, and the superior extensor retinaculum. Magnetic resonance imaging and ultrasonography showed clear thicknening (2.05 mm) of the oblique superomedial band of the inferior extensor retinaculum. Sonopalpation was performed to precisely evaluate/confirm the site of maximum pain. Foot function index (FFI) score was 42. RESULTS: Subsequently, the patient was prescribed fascial manipulation, and he had clinical improvement after the first session (FFI: 21). At 1-month follow-up, the patient was still asymptomatic without any functional limitation (FFI: 24). US imaging confirmed the decreased thickness of the oblique superomedial band of the extensor retinaculum (1.35 mm). CONCLUSION: Fascial Manipulation® appears to be a useful tool to reduce thickness, stiffness, and pain in this case as displayed by the ultrasound Imaging.


Assuntos
Tornozelo , Osteoartrite , Masculino , Humanos , Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/diagnóstico por imagem , Ultrassonografia , Fáscia/diagnóstico por imagem , Dor
3.
Anim Cogn ; 27(1): 13, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38429533

RESUMO

Chronic pain in humans is associated with impaired working memory but it is not known whether this is the case in long-lived companion animals, such as dogs, who are especially vulnerable to developing age-related chronic pain conditions. Pain-related impairment of cognitive function could have detrimental effects on an animal's ability to engage with its owners and environment or to respond to training or novel situations, which may in turn affect its quality of life. This study compared the performance of 20 dogs with chronic pain from osteoarthritis and 21 healthy control dogs in a disappearing object task of spatial working memory. Female neutered osteoarthritic dogs, but not male neutered osteoarthritic dogs, were found to have lower predicted probabilities of successfully performing the task compared to control dogs of the same sex. In addition, as memory retention interval in the task increased, osteoarthritic dogs showed a steeper decline in working memory performance than control dogs. This suggests that the effects of osteoarthritis, and potentially other pain-related conditions, on cognitive function are more clearly revealed in tasks that present a greater cognitive load. Our finding that chronic pain from osteoarthritis may be associated with impaired working memory in dogs parallels results from studies of human chronic pain disorders. That female dogs may be particularly prone to these effects warrants further investigation.


Assuntos
Dor Crônica , Doenças do Cão , Osteoartrite , Humanos , Cães , Feminino , Animais , Memória de Curto Prazo , Dor Crônica/veterinária , Qualidade de Vida , Memória Espacial , Osteoartrite/complicações , Osteoartrite/veterinária
4.
J Orthop Surg Res ; 19(1): 156, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429742

RESUMO

Heat-shock protein beta1 (HSPB1) is a member of the small HSP family, downregulated in osteoarthritis (OA) chondrocytes and demonstrated the capacity to serve as an RNA-binding protein (RBP). This work aimed to explore the profile of HSPB1 bound RNA and reveal the potential regulation mechanism of HSPB1 in OA. In this work, we captured an unbiased HSPB1-RNA interaction map in Hela cells using the iRIP-seq. The results demonstrated that HSPB1 interacted with plentiful of mRNAs and genomic location toward the CDS region. Functional enrichment of HSPB1-related peaks showed the involvement in gene expression, translation initiation, cellular protein metabolic process, and nonsense-mediated decay. HOMER software analysis showed that HSPB1 bound peaks were over-represented in GAGGAG sequences. In addition, ABLIRC and CIMS algorithm indicated that HSPB1 bound to AU-rich motifs and the proportion of AU-rich peaks in 3' UTR were slightly higher than that in other regions. Moreover, HSPB1-binding targets analysis revealed several gens were associated with OA including EGFR, PLEC, COL5A1, and ROR2. The association of OA-related mRNAs to HSPB1 was additionally confirmed in OA tissues by the quantitative RIP-PCR experiments. Further experiment demonstrated the downregulation of HSPB1 in OA tissues. In conclusion, our current study confirmed HSPB1 as an RNA-binding protein and revealed its potential function in the pathological process of OA, providing a reliable insight to further investigate the molecular regulation mechanism of HSPB1 in OA.


Assuntos
Proteínas de Choque Térmico , Osteoartrite , Humanos , Proteínas de Choque Térmico/genética , Células HeLa , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regiões 3' não Traduzidas/genética , Osteoartrite/metabolismo , Chaperonas Moleculares/genética
5.
Musculoskeletal Care ; 22(1): e1873, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38453169

RESUMO

INTRODUCTION: Osteoarthritis is the commonest form of chronic joint pain, which patients often self-manage before seeking healthcare advice. Patients frequently seek advice from community pharmacies, and a recent policy has recommended integrating community pharmacies into long-term condition pathways. This study explored community pharmacy teams' (CPs) and other healthcare professionals' (HCPs) views on community pharmacies providing an extended role for osteoarthritis management, identifying potential barriers and facilitators to this. METHODS: A multi-methods study comprising surveys of CPs and other HCPs, followed by qualitative interviews. Descriptive statistics were used in an exploratory analysis of the survey data. Qualitative data were analysed using reflexive thematic analysis and the identified barriers and facilitators were mapped to the Theoretical Domains Framework. RESULT: CPs and other HCPs in the surveys and interviews reported that an extended role for osteoarthritis management could include: a subjective assessment, explaining the joint problem and its treatment, medication management and support for self-care. There was less consensus on diagnosing the problem as OA and completing an objective assessment. A key facilitator was training to deliver the role, whilst barriers were high workload and lack of access to General Practitioner medical records. DISCUSSION: Acceptable elements of an extended community pharmacy role for osteoarthritis centre around the provision of information, advice on medication and supported self-management. CONCLUSION: CPs are well placed to contribute towards evidenced-based osteoarthritis management. Feasibility testing of delivering the extended role is needed and future implementation requires training for CPs and raising public awareness of the extended role.


Assuntos
Serviços Comunitários de Farmácia , Osteoartrite , Farmácias , Farmácia , Humanos , Atitude do Pessoal de Saúde , Farmacêuticos , Osteoartrite/tratamento farmacológico
6.
Stem Cell Res Ther ; 15(1): 70, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454524

RESUMO

BACKGROUND: Initially discovered for its ability to regenerate ear holes, the Murphy Roth Large (MRL) mouse has been the subject of multiple research studies aimed at evaluating its ability to regenerate other body tissues and at deciphering the mechanisms underlying it. These enhanced abilities to regenerate, retained during adulthood, protect the MRL mouse from degenerative diseases such as osteoarthritis (OA). Here, we hypothesized that mesenchymal stromal/stem cells (MSC) derived from the regenerative MRL mouse could be involved in their regenerative potential through the release of pro-regenerative mediators. METHOD: To address this hypothesis, we compared the secretome of MRL and BL6 MSC and identified several candidate molecules expressed at significantly higher levels by MRL MSC than by BL6 MSC. We selected one candidate, Plod2, and performed functional in vitro assays to evaluate its role on MRL MSC properties including metabolic profile, migration, and chondroprotective effects. To assess its contribution to MRL protection against OA, we used an experimental model for osteoarthritis induced by collagenase (CiOA). RESULTS: Among the candidate molecules highly expressed by MRL MSC, we focused our attention on procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2). Plod2 silencing induced a decrease in the glycolytic function of MRL MSC, resulting in the alteration of their migratory and chondroprotective abilities in vitro. In vivo, we showed that Plod2 silencing in MRL MSC significantly impaired their capacity to protect mouse from developing OA. CONCLUSION: Our results demonstrate that the chondroprotective and therapeutic properties of MRL MSC in the CiOA experimental model are in part mediated by PLOD2.


Assuntos
Células-Tronco Mesenquimais , Osteoartrite , Animais , Camundongos , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/genética , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo
7.
Elife ; 122024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466626

RESUMO

This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation in mice resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.


Assuntos
Cartilagem Articular , Osteoartrite , Resiliência Psicológica , Humanos , Coelhos , Animais , Camundongos , Cartilagem Articular/metabolismo , Osteoartrite/metabolismo , Envelhecimento , Polissacarídeos/metabolismo , Modelos Animais de Doenças
8.
Funct Integr Genomics ; 24(2): 54, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38467932

RESUMO

Despite substantial progress in clinical trials of osteoarthritis (OA) gene therapy, the prevalence of OA is still on the rise. MiRNAs have a potential biomarker and therapeutic target for OA. OA cartilage and chondrosarcoma cells were studied to determine the role of miR-29a-3p and PTEN. OA cartilage and human chondrosarcoma cells (SW1353) were obtained. miR-29a-3p and PTEN signature expression was determined by RT-qPCR. The binding relationship between miR-29a-3p and PTEN was investigated by dual-luciferase reporter gene and western blot assay. TUNEL, immunohistochemistry, CCK-8, and flow cytometry were utilized to determine the proliferation and apoptosis of SW1353 cells. This study indicated downregulation of miR-29a-3p expression and upregulation of PTEN expression in human OA primary chondrocytes or OA tissue samples, compared with the normal cartilage cells or tissues. PTEN expression was negatively correlated with miR-29a-3p expression, and miR-29a-3p targeted PTEN mechanistically. miR-29a-3p reduced SW1353 cell activity and proliferation and promoted cell apoptosis. However, the aforementioned effects could be reversed by downregulating PTEN. miR-29a-3p can stimulate chondrocyte proliferation and inhibit apoptosis by inhibiting PTEN expression.


Assuntos
Neoplasias Ósseas , Condrossarcoma , MicroRNAs , Osteoartrite , Humanos , Apoptose/genética , Proliferação de Células/genética , Condrossarcoma/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/genética , Tensinas
9.
BMC Public Health ; 24(1): 758, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468219

RESUMO

BACKGROUND: The relationship between the triglyceride glucose (TyG) index and osteoarthritis (OA) remains unclear. The objective of this study was to examine potential associations between an elevated TyG index and an increased risk of OA prevalence. METHODS: 3,921 participants with OA from the National Health and Nutrition Examination Survey (2015-2020) were included in this study. Participants were categorized into quartiles based on TyG index, which was determined using the formula: Ln [triglyceride (mg/dL) fasting blood glucose (mg/dL)/2]. Weighted multivariable regression, subgroup analyses, and threshold effect analyses were performed to calculate the independent association between TyG index and OA. RESULTS: A total of 25,514 people were enrolled, with a mean TyG index of 8.48 ± 0.65. The results of multivariable logistic regression analysis after full adjustment showed a significant association between higher TyG index values and an increased risk of OA. Specifically, each incremental unit increase in the TyG index was associated with a 634% higher risk of OA [OR = 7.34; 95% CI: 2.25, 23.93; p = 0.0010]. Based on interaction tests, age, gender, BMI, and smoking status did not significantly affect the relationship between the TyG index and OA, while diabetes showed a stronger positive correlation between the TyG index and OA. CONCLUSION: An increased risk of OA was associated with a higher TyG index. TyG could be a valuable predictor of OA and offer novel perspectives on the assessment and treatment of OA.


Assuntos
Glucose , Osteoartrite , Humanos , Inquéritos Nutricionais , Osteoartrite/epidemiologia , Triglicerídeos , Glicemia
10.
J Orthop Surg Res ; 19(1): 178, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468339

RESUMO

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease characterized by persistent articular cartilage degeneration and synovitis. Oxymatrine (OMT) is a quinzolazine alkaloid extracted from the traditional Chinese medicine, matrine, and possesses anti-inflammatory properties that may help regulate the pathogenesis of OA; however, its mechanism has not been elucidated. This study aimed to investigate the effects of OMT on interleukin-1ß (IL-1ß)-induced damage and the potential mechanisms of action. METHODS: Chondrocytes were isolated from Sprague-Dawley rats. Toluidine blue and Collagen II immunofluorescence staining were used to determine the purity of the chondrocytes. Thereafter, the chondrocytes were subjected to IL-1ß stimulation, both in the presence and absence of OMT, or the autophagy inhibitor 3-methyladenine (3-MA). Cell viability was assessed using the MTT assay and SYTOX Green staining. Additionally, flow cytometry was used to determine cell apoptosis rate and reactive oxygen species (ROS) levels. The protein levels of AKT, mTOR, LC3, P62, matrix metalloproteinase-13, and collagen II were quantitatively analyzed using western blotting. Immunofluorescence was used to assess LC3 expression. RESULTS: OMT alleviated IL-1ß-induced damage in chondrocytes, by increasing the survival rate, reducing the apoptosis rates of chondrocytes, and preventing the degradation of the cartilage matrix. In addition, OMT decreased the ROS levels and inhibited the AKT/mTOR signaling pathway while promoting autophagy in IL-1ß treated chondrocytes. However, the effectiveness of OMT in improving chondrocyte viability under IL-1ß treatment was limited when autophagy was inhibited by 3-MA. CONCLUSIONS: OMT decreases oxidative stress and inhibits the AKT/mTOR signaling pathway to enhance autophagy, thus inhibiting IL-1ß-induced damage. Therefore, OMT may be a novel and effective therapeutic agent for the clinical treatment of OA.


Assuntos
Alcaloides , Cartilagem Articular , Matrinas , Osteoartrite , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Condrócitos/metabolismo , Interleucina-1beta/toxicidade , Interleucina-1beta/metabolismo , Osteoartrite/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Cartilagem Articular/metabolismo , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Alcaloides/metabolismo , Autofagia , Colágeno/metabolismo , Apoptose
11.
Sci Rep ; 14(1): 5968, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472231

RESUMO

To delineate the phenotype of erosive hand osteoarthritis (EHOA) in a Spanish population and assess its correlation with metabolic syndrome. We conducted a cross-sectional study using baseline data from the Prospective Cohort of Osteoarthritis from A Coruña (PROCOAC). Demographic and clinical variables, obtained through questionnaires, clinical examinations, and patient analytics, were compared among individuals with hand OA, with and without EHOA. We performed appropriate univariate and multivariate stepwise regression analyses using SPSS v28. Among 1039 subjects diagnosed with hand OA, 303 exhibited EHOA. Multivariate logistic regression analysis revealed associations with inflamed joints, nodular hand OA, and total AUSCAN. Furthermore, the association with a lower prevalence of knee OA remained significant. The influence of metabolic syndrome (MetS) on EHOA patients was analyzed by including MetS as a covariate in the model. It was observed that MetS does not significantly impact the presence of EHOA, maintaining the effect size of other factors. In conclusion, in the PROCOAC cohort, EHOA is associated with nodular hand OA, inflammatory hand OA, and a higher total AUSCAN. However, EHOA is linked to a lower prevalence of knee OA. Importantly, in our cohort, no relationship was found between EHOA and MetS.


Assuntos
Síndrome Metabólica , Osteoartrite , Humanos , Estudos Transversais , Síndrome Metabólica/complicações , Estudos Prospectivos , Osteoartrite/complicações , Mãos
12.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473759

RESUMO

Osteoarthritis (OA) causes joint pain and disability due to the abnormal production of inflammatory cytokines and reactive oxygen species (ROS) in chondrocytes, leading to cell death and cartilage matrix destruction. Selenium (Se) intake can protect cells against oxidative damage. It is still unknown whether Se supplementation is beneficial for OA. This study investigated the effects of Se on sodium iodoacetate (MIA)-imitated OA progress in human chondrocyte cell line (SW1353 cells) and rats. The results showed that 0.3 µM of Se treatment could protect SW1353 cells from MIA-induced damage by the Nrf2 pathway by promoting the gene expression of glutathione-synthesis-related enzymes such as the glutamate-cysteine ligase catalytic subunit, the glutamate-cysteine ligase modifier subunit, and glutathione synthetase. In addition, glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase expressions are also elevated to eliminate excessive ROS production. Moreover, Se could downregulate NF-κB, leading to a decrease in cytokines, matrix proteases, and glycosaminoglycans. In the rats, MIA-induced cartilage loss was lessened after 2 weeks of Se supplementation by oral gavage; meanwhile, glutathione synthesis was increased, and the expressions of pro-inflammatory cytokines were decreased. These results suggest that Se intake is beneficial for OA due to its effects of decreasing cartilage loss by enhancing antioxidant capacity and reducing inflammation.


Assuntos
Cartilagem Articular , Osteoartrite , Selênio , Humanos , Ratos , Animais , NF-kappa B/metabolismo , Condrócitos/metabolismo , Selênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Osteoartrite/metabolismo , Estresse Oxidativo , Citocinas/metabolismo , Glutationa/metabolismo , Cartilagem Articular/metabolismo
13.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474288

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease mostly affecting the elderly population. It is characterized by cognitive decline that occurs due to impaired neurotransmission and neuronal death. Even though deposition of amyloid beta (Aß) peptides and aggregation of hyperphosphorylated TAU have been established as major pathological hallmarks of the disease, other factors such as the interaction of genetic and environmental factors are believed to contribute to the development and progression of AD. In general, patients initially present mild forgetfulness and difficulty in forming new memories. As it progresses, there are significant impairments in problem solving, social interaction, speech and overall cognitive function of the affected individual. Osteoarthritis (OA) is the most recurrent form of arthritis and widely acknowledged as a whole-joint disease, distinguished by progressive degeneration and erosion of joint cartilage accompanying synovitis and subchondral bone changes that can prompt peripheral inflammatory responses. Also predominantly affecting the elderly, OA frequently embroils weight-bearing joints such as the knees, spine and hips leading to pains, stiffness and diminished joint mobility, which in turn significantly impacts the patient's standard of life. Both infirmities can co-occur in older adults as a result of independent factors, as multiple health conditions are common in old age. Additionally, risk factors such as genetics, lifestyle changes, age and chronic inflammation may contribute to both conditions in some individuals. Besides localized peripheral low-grade inflammation, it is notable that low-grade systemic inflammation prompted by OA can play a role in AD pathogenesis. Studies have explored relationships between systemic inflammatory-associated diseases like obesity, hypertension, dyslipidemia, diabetes mellitus and AD. Given that AD is the most common form of dementia and shares similar risk factors with OA-both being age-related and low-grade inflammatory-associated diseases, OA may indeed serve as a risk factor for AD. This work aims to review literature on molecular mechanisms linking OA and AD pathologies, and explore potential connections between these conditions alongside future prospects and innovative treatments.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Osteoartrite , Humanos , Idoso , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/genética , Estudos Transversais , Multimorbidade , Inflamação
14.
Sci Rep ; 14(1): 5078, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429394

RESUMO

Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process of osteoarthritis (OA). Herein, we investigated the protective effect of moderate mechanical stress on chondrocyte ferroptosis and further revealed the internal molecular mechanism. Intra-articular injection of sodium iodoacetate (MIA) was conducted to induce the rat model of OA in vivo, meanwhile, interleukin-1 beta (IL-1ß) was treated to chondrocytes to induce the OA cell model in vitro. The OA phenotype was analyzed by histology and microcomputed tomography, the ferroptosis was analyzed by transmission electron microscope and immunofluorescence. The expression of ferroptosis and cartilage metabolism-related factors was analyzed by immunohistochemical and Western blot. Animal experiments revealed that moderate-intensity treadmill exercise could effectively reduce chondrocyte ferroptosis and cartilage matrix degradation in MIA-induced OA rats. Cell experiments showed that 4-h cyclic tensile strain intervention could activate Nrf2 and inhibit the NF-κB signaling pathway, increase the expression of Col2a1, GPX4, and SLC7A11, decrease the expression of MMP13 and P53, thereby restraining IL-1ß-induced chondrocyte ferroptosis and degeneration. Inhibition of NF-κB signaling pathway relieved the chondrocyte ferroptosis and degeneration. Meanwhile, overexpression of NF-κB by recombinant lentivirus reversed the positive effect of CTS on chondrocytes. Moderate mechanical stress could activate the Nrf2 antioxidant system, inhibit the NF-κB p65 signaling pathway, and inhibit chondrocyte ferroptosis and cartilage matrix degradation by regulating P53, SLC7A11, and GPX4.


Assuntos
Ferroptose , Osteoartrite , Estresse Mecânico , Animais , Ratos , Condrócitos/metabolismo , Interleucina-1beta/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , NF-kappa B/fisiologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Microtomografia por Raio-X , Fator de Transcrição RelA/metabolismo , Fator de Transcrição RelA/fisiologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/fisiologia
15.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 244-249, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38430015

RESUMO

Osteoarthritis (OA) is a major disease that causes disability in middle-aged and elderly people. A comprehensive understanding of its pathogenesis is of great significance in finding new clinical diagnosis and treatment schemes. The role of Semaphorin 3A (Sema3A) in OS has attracted attention recently, and the purpose of this study is to analyze the mechanisms underlying its impact on OS. First, a rat model of OS was established. Hematoxylin-eosin (HE) and TUNEL staining showed that the modeled rats presented typical pathological manifestations of OS, confirming the success of the modeling. Sema3A was significantly underexpressed in OS rats. Subsequently, Sema3A abnormal expression vectors were constructed to intervene in chondrocytes isolated from OS rats. It was found that the proliferation of chondrocytes was decreased, the apoptosis was increased, and the mitochondrial damage and autophagy were intensified after silencing Sema3A expression, while the above pathological processes were reversed when Sema3A expression was increased. In conclusion, Sema3A has an important influence on the pathological progression of OS, and molecular therapies targeting to increase Sema3A expression may become a new treatment for OS in the future.


Assuntos
Osteoartrite , Semaforina-3A , Animais , Ratos , Apoptose/genética , Condrócitos/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Semaforina-3A/genética , Semaforina-3A/metabolismo
16.
J Orthop Surg Res ; 19(1): 158, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429844

RESUMO

BACKGROUND: Osteoarthritis (OA) is a joint disease characterized by inflammation and progressive cartilage degradation. Chondrocyte apoptosis is the most common pathological feature of OA. Interleukin-1ß (IL-1ß), a major inflammatory cytokine that promotes cartilage degradation in OA, often stimulates primary human chondrocytes in vitro to establish an in vitro OA model. Moreover, IL-1ß is involved in OA pathogenesis by stimulating the phosphoinositide-3-kinase (PI3K)/Akt and mitogen-activated protein kinases pathways. The G-protein-coupled receptor, cc chemokine receptor 10 (CCR10), plays a vital role in the occurrence and development of various malignant tumors. However, the mechanism underlying the role of CCR10 in the pathogenesis of OA remains unclear. We aimed to evaluate the protective effect of CCR10 on IL-1ß-stimulated CHON-001 cells and elucidate the underlying mechanism. METHODS: The CHON-001 cells were transfected with a control small interfering RNA (siRNA) or CCR10-siRNA for 24 h, and stimulated with 10 ng/mL IL-1ß for 12 h to construct an OA model in vitro. The levels of CCR10, cleaved-caspase-3, MMP-3, MMP-13, Collagen II, Aggrecan, p-PI3K, PI3K, p-Akt, Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), and mTOR were detected using quantitative reverse transcription polymerase chain reaction and western blotting. Viability, cytotoxicity, and apoptosis of CHON-001 cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase assay (LDH), and flow cytometry analysis, respectively. Inflammatory cytokines (TNF-α, IL-6, and IL-8) were assessed using enzyme-linked immunosorbent assay. RESULTS: Level of CCR10 was substantially higher in the IL-1ß-stimulated CHON-001 cells than that in the control group, whereas CCR10 was down-regulated in the CCR10-siRNA transfected CHON-001 cells compared to that in the control-siRNA group. Notably, CCR10 inhibition alleviated IL-1ß-induced inflammatory injury in the CHON-001 cells, as verified by enhanced cell viability, inhibited LDH release, reduced apoptotic cells, and cleaved-caspase-3 expression. Meanwhile, IL-1ß induced the release of tumor necrosis factor alpha, IL-6, and IL-8, increase of MMP-3 and MMP-13, and decrease of Collagen II and Aggrecan in the CHON-001 cells, which were reversed by CCR10-siRNA. However, these effects were reversed upon PI3K agonist 740Y-P treatment. Further, IL-1ß-induced PI3K/Akt/mTOR signaling pathway activation was inhibited by CCR10-siRNA, which was increased by 740Y-P treatment. CONCLUSION: Inhibition of CCR10 alleviates IL-1ß-induced chondrocytes injury via PI3K/Akt/mTOR pathway inhibition, suggesting that CCR10 might be a promising target for novel OA therapeutic strategies.


Assuntos
Osteoartrite , Fragmentos de Peptídeos , Fosfatidilinositol 3-Quinase , Receptores do Fator de Crescimento Derivado de Plaquetas , Humanos , Agrecanas , Caspase 3 , Colágeno , Citocinas , Interleucina-6 , Interleucina-8 , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 3 da Matriz , Osteoartrite/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositóis , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CCR10 , RNA Interferente Pequeno , Serina-Treonina Quinases TOR
17.
Sci Adv ; 10(10): eadk6084, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457498

RESUMO

The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.


Assuntos
Cartilagem Articular , Nanopartículas , Osteoartrite , Ratos , Animais , Óxido de Magnésio/farmacologia , Magnésio/farmacologia , Fosfatidilinositol 3-Quinases , Osteoartrite/tratamento farmacológico
18.
J Zhejiang Univ Sci B ; 25(3): 197-211, 2024 Mar 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38453635

RESUMO

Osteoarthritis (OA), characterized by cartilage degeneration, synovial inflammation, and subchondral bone remodeling, is among the most common musculoskeletal disorders globally in people over 60 years of age. The initiation and progression of OA involves the abnormal metabolism of chondrocytes as an important pathogenic process. Cartilage degeneration features mitochondrial dysfunction as one of the important causative factors of abnormal chondrocyte metabolism. Therefore, maintaining mitochondrial homeostasis is an important strategy to mitigate OA. Mitophagy is a vital process for autophagosomes to target, engulf, and remove damaged and dysfunctional mitochondria, thereby maintaining mitochondrial homeostasis. Cumulative studies have revealed a strong association between mitophagy and OA, suggesting that the regulation of mitophagy may be a novel therapeutic direction for OA. By reviewing the literature on mitophagy and OA published in recent years, this paper elaborates the potential mechanism of mitophagy regulating OA, thus providing a theoretical basis for studies related to mitophagy to develop new treatment options for OA.


Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Pessoa de Meia-Idade , Idoso , Mitofagia , Inflamação/metabolismo , Condrócitos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia
19.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(3): 263-266, 2024 Mar 09.
Artigo em Chinês | MEDLINE | ID: mdl-38432659

RESUMO

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease of temporomandibular joint, which has a high incidence and affects the quality of patients' life. While the pathogenesis of TMJOA remains unclear. It has been found that angiogenesis is involved in the development of TMJOA and it is closely related to the degradation of articular cartilage matrix, subchondral ossification, osteophyte formation and pain. This article reviews the recent advances in the study of angiogenesis in TMJOA, and provides a prospect for the treatment of TMJOA.


Assuntos
Cartilagem Articular , Osteoartrite , Transtornos da Articulação Temporomandibular , Humanos , Transtornos da Articulação Temporomandibular/terapia , Articulação Temporomandibular/patologia , Osteoartrite/patologia
20.
BMC Geriatr ; 24(1): 242, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459429

RESUMO

BACKGROUND: In light of the aging population, increasingly suffering from the metabolic syndrome (MS), strategies need to be developed to address global public health challenges known to be associated with MS such as arthritis. As physical activity (PA) may play a crucial role in tackling those challenges, this study aimed to determine the association between the number of MS risk factors, PA and arthritis in people ≥ 50 years old. METHODS: Data from the Survey of Health, Ageing, and Retirement in Europe (SHARE) were used to estimate the prevalence of arthritis and MS risk factors in the European population ≥ 50 years and to evaluate the associations between MS risk factors, PA and arthritis. Binary logistic regression was performed to calculate the odds ratio of different factors. RESULTS: 73,125 participants were included in the analysis. 55.75% of patients stated at least one of the three MS risk factors. The prevalence of rheumatoid arthritis (RA) and osteoarthritis (OA)/other rheumatism among ≥ 50 years population was 10.19% and 19.32% respectively. Females showed a higher prevalence of arthritis than males. Prevalence did not differ between groups with different levels of PA. Arthritis prevalence was positively correlated with the number of MS risk factors (P < 0.01) but not with PA (P > 0.05). CONCLUSION: Middle-aged and older Europeans with multiple comorbidities suffered from RA, OA or other rheumatism more frequently than participants with fewer comorbidities, while the level of physical activity was not associated with the number of metabolic risk factors in patients with RA and OA/other rheumatism.


Assuntos
Artrite Reumatoide , Síndrome Metabólica , Osteoartrite , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Estudos Transversais , Prevalência , Fatores de Risco , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Exercício Físico
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