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1.
Yao Xue Xue Bao ; 51(11): 1711-6, 2016 11.
Artículo en Zh | MEDLINE | ID: mdl-29908114

RESUMEN

To study the role of oleanolic acid on interleukin (IL)-1ß-stimulated expression of inflammatory cytokines, and to explore its anti-inflammatory mechanism in SW982 cells, the toxicity of oleanolic acid on SW982 cells was detected by MTT; effects of different concentrations of oleanolic acid(5, 10, 20 µmol·L(-1)) on the expression of inflammatory factors IL-6, IL-8 and matrix metalloproteinase-1 (MMP-1) was tested at protein and m RNA levels. The study was performed in IL-1ß-stimulated SW982 cells together with enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative PCR (real-time PCR) methods; the influence of oleanolic acid on the phosphorylation of mitogen-activated protein kinase (MAPK), phosphatidyl inositol-3-kinase/Akt (PI3K/Akt) and nuclear transcription factor-κB (NF-κB) signaling pathways related protein was analyzed by Western blot. Results showed that different concentrations of oleanolic acid(≤40 µmol·L(-1)) were almost non-toxicity to SW982 cells; oleanolic acid significantly inhibited the expression of inflammatory factors in a dose-dependent manner; oleanolic acid restrained extracellular signal-related kinase (ERK), p38, c-jun N-terminal kinase (JNK) and Akt protein phosphorylation and IκB-α protein degradation obviously. The inhibition effect of oleanolic acid on inflammatory factors stimulated by IL-1ß may be worked through MAPK, PI3K/Akt and NF-κB signaling pathways.


Asunto(s)
Antiinflamatorios/farmacología , Inflamación/metabolismo , Ácido Oleanólico/farmacología , Sarcoma Sinovial/metabolismo , Línea Celular , Citocinas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-1beta/farmacología , Metaloproteinasa 1 de la Matriz/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sarcoma Sinovial/tratamiento farmacológico , Transducción de Señal , Factor de Transcripción ReIA/metabolismo
2.
Front Endocrinol (Lausanne) ; 12: 657953, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34054729

RESUMEN

Neural cell adhesion molecule (NCAM) is involved in cell multi-directional differentiation, but its role in osteoblast differentiation is still poorly understood. In the present study, we investigated whether and how NCAM regulates osteoblastic differentiation. We found that NCAM silencing inhibited osteoblast differentiation in pre-osteoblastic MC3T3-E1 cells. The function of NCAM was further confirmed in NCAM-deficient mesenchymal stem cells (MSCs), which also had a phenotype with reduced osteoblastic potential. Moreover, NCAM silencing induced decrease of Wnt/ß-catenin and Akt activation. The Wnt inhibitor blocked osteoblast differentiation, and the Wnt activator recovered osteoblast differentiation in NCAM-silenced MC3T3-E1 cells. We lastly demonstrated that osteoblast differentiation of MC3T3-E1 cells was inhibited by the PI3K-Akt inhibitor. In conclusion, these results demonstrate that NCAM silencing inhibited osteoblastic differentiation through inactivation of Wnt/ß-catenin and PI3K-Akt signaling pathways.


Asunto(s)
Diferenciación Celular , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Osteoblastos/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animales , Línea Celular , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Moléculas de Adhesión de Célula Nerviosa/genética , Osteoblastos/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal , Proteínas Wnt/genética , beta Catenina/genética
3.
Stem Cells Transl Med ; 9(2): 273-283, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31742919

RESUMEN

Chondrocyte hypertrophy-like change is an important pathological process of osteoarthritis (OA), but the mechanism remains largely unknown. Neural cell adhesion molecule (NCAM) is highly expressed and involved in the chondrocyte differentiation of mesenchymal stem cells (MSCs). In this study, we found that NCAM deficiency accelerates chondrocyte hypertrophy in articular cartilage and growth plate of OA mice. NCAM deficiency leads to hypertrophic chondrocyte differentiation in both murine MSCs and chondrogenic cells, in which extracellular signal-regulated kinase (ERK) signaling plays an important role. Moreover, NCAM expression is downregulated in an interleukin-1ß-stimulated OA cellular model and monosodium iodoacetate-induced OA rats. Overexpression of NCAM substantially inhibits hypertrophic differentiation in the OA cellular model. In conclusion, NCAM could inhibit hypertrophic chondrocyte differentiation of MSCs by inhibiting ERK signaling and reduce chondrocyte hypertrophy in experimental OA model, suggesting the potential utility of NCAM as a novel therapeutic target for alleviating chondrocyte hypertrophy of OA.


Asunto(s)
Condrocitos/metabolismo , Condrogénesis/fisiología , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Osteoartritis/patología , Animales , Diferenciación Celular , Humanos , Ratones , Ratas , Ratas Wistar , Transfección
4.
Front Pharmacol ; 9: 910, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30174601

RESUMEN

Background and purpose: Fengshi Gutong capsule (FSGTC), a traditional herbal formula, has been used clinically in China for the treatment of arthritis. However, the mechanism underlying the therapeutic effects of FSGTC on osteoarthritis (OA) has not been elucidated. The present study investigated the function and mechanisms of FSGTC in rat OA model and interleukin (IL)-1ß-stimulated synovial cells. Materials and methods: Rat OA model was established by intra-articular injection containing 4% papain. IL-1ß-induced SW982 cells were used as an OA cell model. Safranin-O-Fast green (S-O) and hematoxylin-eosin (HE) stainings were used to observe the changes in cartilage morphology. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qPCR) detected the expression of inflammatory cytokines. In addition, molecular mechanisms were analyzed by Western blot in the OA cell model. Results: FSGTC treatment significantly relieved the degeneration of cartilage and reduced the contents of tumor necrosis factor-α (TNF-α) and IL-6 in the serum in papain-induced OA rats. FSGTC also reduced the protein and mRNA levels of IL-6 and IL-8 in IL-1ß-stimulated SW982 cells. Moreover, it inhibited the phosphorylation levels of ERK (extracellular signal-related kinase), JNK (c-Jun N-terminal kinase), p38, Akt (protein kinase B), and c-Jun. It also decreased the extent of IκBα degradation and p65 protein translocation into the nucleus. Conclusion: The current data confirmed the protective effects of FSGTC in the rat and OA cell models. The results suggested that FSGTC reduced the production of inflammatory mediators via restraining the activation of mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-κB), activator protein-1 (AP-1), and Akt.

5.
Int Immunopharmacol ; 50: 224-229, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28692879

RESUMEN

The present study shows the basis for the anti-inflammatory effects of pitavastatin in interleukin (IL)-1ß-induced human synovial cells. The SW982 cells were pretreated with pitavastatin at different concentrations (5µM and 10µM), followed by IL-1ß (10ng/mL) stimulation. The results showed that pitavastatin inhibited the expression of inflammatory mediators IL-6 and IL-8. Furthermore, pitavastatin inhibited the phosphorylation of p38, extracellular signal-related kinase (ERK), c-jun N-terminal kinase (JNK) and protein kinase B (Akt). It also suppressed the degradation of I kappa B alpha and blocked p65 translocation into the nucleus. These findings suggest that the mechanism underlying the inhibitory effects of pitavastatin on IL-1ß-induced IL-6 and IL-8 release might be mediated by the suppression of mitogen-activated protein kinase (MAPK), Akt, and nuclear factor-κB (NF-κB) signaling pathways. These results may also indicate that pitavastatin may be potentially utilized as an effective therapeutic agent for the treatment of osteoarthritis.


Asunto(s)
Antiinflamatorios/farmacología , Osteoartritis/tratamiento farmacológico , Quinolinas/farmacología , Sinoviocitos/efectos de los fármacos , Línea Celular , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-1beta/inmunología , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Sistema de Señalización de MAP Quinasas , FN-kappa B/metabolismo , Sinoviocitos/patología
6.
Food Funct ; 7(11): 4516-4522, 2016 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-27713966

RESUMEN

Hydroxysafflor yellow A (HSYA), the main active ingredient in medical and edible dual purpose plant safflower, is reported to have multiple bioactivities. In the present study, the anti-inflammatory effects of HSYA and the underlying mechanisms were investigated in interleukin (IL)-1ß-induced SW982 human synovial cells. The cells were pretreated with HSYA at various concentrations (2.5, 10 and 40 µM) followed by IL-1ß (10 ng mL-1) stimulation. HSYA significantly inhibited the expression of IL-6, IL-8 and matrix metalloproteinase (MMP)-1 in IL-1ß-stimulated SW982 cells. HSYA also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), p65 and c-Jun. It also suppressed the degradation of IκBα and blocked p65 translocation into the nucleus. These results indicate that the inhibitory effects of HSYA on IL-1ß-induced IL-6, IL-8 and MMP-1 release might be mediated via suppression of ERK, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) signaling pathways. The present data support the potential role of HSYA as an effective therapeutic agent in osteoarthritis.


Asunto(s)
Chalcona/análogos & derivados , Citocinas/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Metaloproteinasa 1 de la Matriz/metabolismo , Quinonas/farmacología , Membrana Sinovial/citología , Línea Celular , Supervivencia Celular , Chalcona/química , Chalcona/farmacología , Citocinas/genética , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Interleucina-1beta/farmacología , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Metaloproteinasa 1 de la Matriz/genética , Estructura Molecular , FN-kappa B/genética , FN-kappa B/metabolismo , Quinonas/química , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo
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