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Joint pain and osteoarthritis can occur as coronavirus disease 2019 (COVID-19) sequelae after infection. However, little is known about the damage to articular cartilage. Here we illustrate knee joint damage after wild-type, Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vivo. Rapid joint injury with cystic lesions at the osteochondral junction was observed in two patients with post-COVID osteoarthritis and recapitulated in a golden Syrian hamster model. SARS-CoV-2-activated endothelin-1 signalling increased vascular permeability and caused viral spike proteins leakage into the subchondral bone. Osteoclast activation, chondrocyte dropout and cyst formation were confirmed histologically. The US Food and Drug Administration-approved endothelin receptor antagonist, macitentan, mitigated cystic lesions and preserved chondrocyte number in the acute phase of viral infection in hamsters. Delayed macitentan treatment at post-acute infection phase alleviated chondrocyte senescence and restored subchondral bone loss. It is worth noting that it could also attenuate viral spike-induced joint pain. Our work suggests endothelin receptor blockade as a novel therapeutic strategy for post-COVID arthritis.
Assuntos
COVID-19 , Modelos Animais de Doenças , Antagonistas dos Receptores de Endotelina , Mesocricetus , Osteoartrite , Pirimidinas , SARS-CoV-2 , Animais , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Humanos , COVID-19/virologia , COVID-19/complicações , COVID-19/metabolismo , COVID-19/patologia , Osteoartrite/tratamento farmacológico , Osteoartrite/virologia , Osteoartrite/patologia , Osteoartrite/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Antagonistas dos Receptores de Endotelina/farmacologia , Antagonistas dos Receptores de Endotelina/uso terapêutico , Sulfonamidas/farmacologia , Cricetinae , Masculino , Tratamento Farmacológico da COVID-19 , Condrócitos/virologia , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/virologia , Cartilagem Articular/metabolismo , Cartilagem Articular/efeitos dos fármacos , Receptores de Endotelina/metabolismo , Endotelina-1/metabolismo , Feminino , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
The coronavirus disease-2019 pandemic reflects the underdevelopment of point-of-care diagnostic technology. Nuclei acid (NA) detection is the "gold standard" method for the early diagnosis of the B.1.1.529 (Omicron) variant of severe acute respiratory syndrome-coronavirus disease-2. Polymerase chain reaction is the main method for NA detection but requires considerable manpower and sample processing taking ≥ 3 h. To simplify the operation processes and reduce the detection time, exonuclease III (Exo III)-aided MoS2 /AIE nanoprobes were developed for rapid and sensitive detection of the oligonucleotides of Omicron. Molybdenum disulfide (MoS2 ) nanosheets with excellent optical absorbance and distinguishable affinity to single-strand and duplex DNAs were applied as quenchers, and aggregation-induced emission (AIE) molecules with high luminous efficiency were designed as donor in fluorescence resonance energy transfer-based nanoprobes. Exo III with catalytic capability was used for signal amplification to increase the sensitivity of detection. The composite nanoprobes detected the mutated nucleocapsid (N)-gene and spike (S)-gene oligonucleotides of Omicron within 40 min with a limit of detection of 4.7 pM, and showed great potential for application in community medicine.
Assuntos
Técnicas Biossensoriais , COVID-19 , Exodesoxirribonucleases , Humanos , Oligonucleotídeos , SARS-CoV-2/genética , Molibdênio , Técnicas Biossensoriais/métodos , COVID-19/diagnósticoRESUMO
Objective: Literature examining the relationship between elevated blood pressure and osteoarthritis (OA) has yielded conflicting results. This study aimed to systematically review the relationship between hypertension and OA in both load-bearing and non-load-bearing joints. Methods: A systematic literature search was performed on Embase, Emcare, MEDLINE and Ovid Nursing Database. The associations between hypertension and OA development in knees, hips and hands were analysed by calculating the odds ratio (OR). Results: A total of 26 studies with 97,960 participants were included. The overall odds of having OA significantly increased in the people with hypertension compared to the normotensive ones (OR â= â1.60, 95%CI â= â1.33, 1.94). The association of hypertension with OA was detected in knee (OR â= â1.62, 95%CI â= â1.32, 1.98), not in hand (OR â= â1.19, 95%CI â= â0.92, 1.53). Moreover, there existed a stronger association of hypertension with radiographic knee OA (OR â= â1.89, 95%CI â= â1.40, 2.54) than symptomatic knee OA (OR â= â1.39, 95%CI â= â1.17, 1.65). The association between hypertension and radiographic knee OA remained statistically significant for the studies that adjusted for body mass index (BMI) (OR â= â1.42, 95%CI â= â1.13, 1.78), and was particularly strong in women (OR â= â2.27, 95%CI â= â1.17, 4.39). Conclusion: A BMI-independent association between hypertension and radiographic knee OA existed with potential sex variation, which warrants further investigations into the underlying genetic, hormonal and environmental factors.The translational potential of this article: Blood pressure has been reported to link with OA for years ago, however, its contribution to OA is still unclear and conflicted in different reports. This review indicated an intimate relationship between hypertension and structural damages of knee OA, rather than simply chronic joint pain, especially in women. This finding not only provides stronger support for further investigations into the causal risk factor, i.e. hypertension, of OA from tissue level to molecular level, but also putting forward a novel thinking in OA pathogenesis and its therapy strategies. Orthopedic translation: This study further strengthen the association between hypertension and radiographic knee OA. It points in a vascular aetiology hypothesis of OA. It might open up a new avenue for repositioning anti-hypertensive medications for osteoarthritis treatment.
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Osteoarthritis (OA) is a prevalent chronic whole-joint disease characterized by low-grade systemic inflammation, degeneration of joint-related tissues such as articular cartilage, and alteration of bone structures that can eventually lead to disability. Emerging evidence has indicated that synovium or articular cartilage-secreted extracellular vesicles (EVs) contribute to OA pathogenesis and physiology, including transporting and enhancing the production of inflammatory mediators and cartilage degrading proteinases. Bioactive components of EVs are known to play a role in OA include microRNA, long non-coding RNA, and proteins. Thus, OA tissues-derived EVs can be used in combination with advanced nanomaterial-based biosensors for the diagnostic assessment of OA progression. Alternatively, mesenchymal stem cell- or platelet-rich plasma-derived EVs (MSC-EVs or PRP-EVs) have high therapeutic value for treating OA, such as suppressing the inflammatory immune microenvironment, which is often enriched by pro-inflammatory immune cells and cytokines that reduce chondrocytes apoptosis. Moreover, those EVs can be modified or incorporated into biomaterials for enhanced targeting and prolonged retention to treat OA effectively. In this review, we explore recently reported OA-related pathological biomarkers from OA joint tissue-derived EVs and discuss the possibility of current biosensors for detecting EVs and EV-related OA biomarkers. We summarize the applications of MSC-EVs and PRP-EVs and discuss their limitations for cartilage regeneration and alleviating OA symptoms. Additionally, we identify advanced therapeutic strategies, including engineered EVs and applying biomaterials to increase the efficacy of EV-based OA therapies. Finally, we provide our perspective on the future of EV-related diagnosis and therapeutic potential for OA treatment.
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Vesículas Extracelulares/metabolismo , Osteoartrite , Medicina de Precisão/métodos , Animais , Biomarcadores/metabolismo , Humanos , Osteoartrite/metabolismo , Osteoartrite/terapiaRESUMO
Osteoarthritis (OA) is one of the rapidly growing disability-associated conditions with population aging worldwide. There is a pressing need for precise diagnosis and timely intervention for OA in the early stage. Current clinical imaging modalities, including pain radiography, magnetic resonance imaging, ultrasound, and optical coherent tomography, are limited to provide structural changes when the damage has been established or advanced. It prompts further endeavors in search of novel functional and molecular imaging, which potentially enables early diagnosis and intervention of OA. A hybrid imaging modality based on photothermal effects, photoacoustic imaging, has drawn wide attention in recent years and has seen a variety of biomedical applications, due to its great performance in yielding high-contrast and high-resolution images from structure to function, from tissue down to molecular levels, from animals to human subjects. Photoacoustic imaging has witnessed gratifying potentials and preliminary effects in OA diagnosis. Regarding the treatment of OA, photothermal-triggered therapy has exhibited its attractions for enhanced therapeutic outcomes. In this narrative review, we will discuss photoacoustic imaging for the diagnosis and monitoring of OA at different stages. Structural, functional, and molecular parameter changes associated with OA joints captured by photoacoustics will be summarized, forming the diagnosis perspective of the review. Photothermal therapy applications related to OA will also be discussed herein. Lastly, relevant clinical applications and its potential solutions to extend photoacoustic imaging to deeper OA situations have been proposed. Although some aspects may not be covered, this mini review provides a better understanding of the diagnosis and treatment of OA with exciting innovations based on tissue photothermal effects. It may also inspire more explorations in the field towards earlier and better theranostics of OA.
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Osteoartrite/diagnóstico , Osteoartrite/terapia , Animais , Liberação Controlada de Fármacos , Elasticidade , Humanos , Peróxido de Hidrogênio/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/fisiopatologia , Técnicas FotoacústicasRESUMO
BACKGROUND: Lycium barbarum polysaccharide (LBP), the most abundant functional component of wolfberry, is considered a potent antioxidant and an anti-ageing substance. This review aims to outline the hallmarks of ageing in the pathogenesis of osteoarthritis (OA), followed by the current understanding of the senolytic effect of LBP and its potential use in the prevention and treatment of OA. This will be discussed through the lens of molecular biology and herbal medicine. METHODS: A literature search was performed from inception to March 2020 using following keywords: "Lycium barbarum polysaccharide", "DNA damage", antioxidant, anti-apoptosis, anti-inflammation, anti-ageing, osteoarthritis, chondrocytes, fibroblasts, osteoblasts, osteoclasts, and "bone mesenchymal stem cell". The initial search yielded 2287 papers, from which 35 studies were selected for final analysis after screening for topic relevancy by the authors. RESULTS: In literature different in vitro and in vivo ageing models are used to demonstrate LBP's ability to reduce oxidative stress, restore mitochondrial function, mitigate DNA damage, and prevent cellular senescence. All the evidence hints that LBP theoretically attenuates senescent cell accumulation and suppresses the senescence-associated secretory phenotype as observed by the reduction in pro-inflammatory cytokines, like interleukin-1beta, and matrix-degrading enzymes, such as MMP-1 and MMP-13. However, there remains a lack of evidence on the disease-modifying effect of LBP in OA, although its chondroprotective, osteoprotective and anti-inflammatory effects were reported. CONCLUSION: Our findings strongly support further investigations into the senolytic effect of LBP in the context of age-related OA.
Assuntos
Envelhecimento , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Osteoartrite/tratamento farmacológico , Osteoartrite/prevenção & controle , Medicamentos de Ervas Chinesas/administração & dosagem , HumanosRESUMO
Osteoarthritis (OA) is a leading cause of chronic pain in the elderly worldwide. Yet current diagnosis and therapy for OA pain are subjective and nonspecific with significant adverse effects. Here, we introduced a theranostic nanoprobe based on molybdenum disulfide nanosheet-coated gold nanorods (MoS2-AuNR) targeting never growth factor (NGF), a key player in pain sensation, for photoacoustic pain imaging and near-infrared (NIR) imaging-guided photothermal analgesic therapy. MoS2 coating significantly improved the photoacoustic and photothermal performance of AuNR. Functionalization of MoS2-AuNR nanoprobes by conjugating with NGF antibody enabled active targeting on painful OA knees in a surgical OA murine model. We observed that our functional nanoprobes accumulated in the OA knee rather than the contralateral intact one, and the amount was correlated with the severity of mechanical allodynia in our mouse model. Under imaging guidance, NIR-excited photothermal therapy could mitigate mechanical allodynia and walking imbalance behavior for both subacute and chronic stages of OA in a preclinical setting. This molecular theranostic approach enabled us to specifically localize the source of OA pain and efficiently block peripheral pain transmission.