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1.
Ann Agric Environ Med ; 27(1): 66-75, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32208582

RESUMO

OBJECTIVE: The aim of the study was to determine the effect of nesfatin-1 on bone properties in female rats in the conditions of developing osteopenia induced by ovariectomy (OVX). MATERIAL AND METHODS: The experiment was performed on 21 female Wistar rats assigned to 3 groups receiving intraperitoneally physiological saline (SHO, OVX-PhS) and nesfatin-1 in dose 2 µg/kg BW of (OVX-NES) once a day for 8 wks. At the end of the experiment, the rats were scanned using the DXA method to determine the body composition, tBMC, and tBMD. The isolated femora and tibia were tested with the DXA method for BMD and BMC, and with the pQCT method for separate analysis of the cortical and trabecular bone tissue. The bone strength parameters were also determined. The immunohistochemical method was used for determination of nesfatin-1 localization in growth cartilage. Bone metabolism markers (osteocalcin, bALP, and NTx) were identified using an ELISA kit. RESULTS: OVX exerts a negative effect on bone tissue. The nesfatin-1 administration influenced positively the DXA parameters of tibia. TvBMD and TbvBMD measured by pQCT in metaphysis of bones were significantly higher in the OVX-NES group than in OVX-PhS. No differences were found in the values of bone strength parameters between SHO and OVX-NES females. Extra- and intracellular immunohistochemical reaction for nesfatin-1 was observed in all zones of growth cartilage, with the strongest reaction detected in the calcifying zone. Nesfatin-1 administration caused a significant increase in the osteocalcin and bALP concentration in relation to the OVX-PhS animals. CONCLUSIONS: The results of the experiment indicate that nesfatin-1 exerts a protective effect on bone tissue properties and can be used in the prevention of osteoporosis.


Assuntos
Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/tratamento farmacológico , Nucleobindinas/farmacologia , Absorciometria de Fóton , Fosfatase Alcalina/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/metabolismo , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Osteocalcina/metabolismo , Ovariectomia , Ratos Wistar , Tíbia/diagnóstico por imagem , Tíbia/efeitos dos fármacos
2.
Chemosphere ; 249: 126537, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32208220

RESUMO

BACKGROUND: As one of the most common endocrine-disrupting chemicals (EDCs), bisphenol A (BPA) is a threat to aquatic ecosystems. Despite a rich literature addressing the adverse effects of BPA on various systems in fish models, the potential impact of parental BPA exposure on offspring pharyngeal cartilage development is poorly understood. METHODS: Adult zebrafish (F0) were exposed to BPA (1.0 µM) or control for 7 days. Eggs (F1) were collected and exposed to BPA (control, 0.05, 0.1, 1, 10 µM) until 120 h post-fertilization. Histomorphometrical essay was used to quantitatively and qualitatively assess the effects of BPA on pharyngeal cartilage development. RNA sequencing (RNA-seq) was used to discover differentially expressed genes (DEGs), and KEGG pathway and GO enrichment analysis were performed to interpret functional ontology. RESULTS: Parental BPA exposure affected hatchability and heart rates of F1 progeny. By pathology analysis, parental BPA exposure caused craniofacial deformity, characterized by wider angles of cartilage elements, disrupted pharyngeal chondrocytes and promoted apoptosis and elongation of head length. RNA-seq suggested that many DEGs were involved in multiple biological processes and signaling pathways; defense responses, reactive oxygen species metabolic process, apoptosis, p53 signaling pathway and MAPK signaling pathway were closely associated with the toxicity of parental BPA exposure. CONCLUSIONS: Parental BPA exposure affected chondrogenesis in the viscerocranium of zebrafish offspring and led to global transcriptomic changes involved in apoptosis, hyperplasia and oxidative stress. These newly identified gene expression patterns, pathways and gene networks of zebrafish eleutheroembryos after early-life waterborne BPA exposure, may lead to severe and permanent morphological and functional consequences.


Assuntos
Compostos Benzidrílicos/toxicidade , Cartilagem/crescimento & desenvolvimento , Disruptores Endócrinos/toxicidade , Fenóis/toxicidade , Peixe-Zebra/fisiologia , Animais , Cartilagem/efeitos dos fármacos , Condrogênese , Ecossistema , Análise de Sequência de RNA , Transcriptoma , Peixe-Zebra/metabolismo
3.
Ann N Y Acad Sci ; 1460(1): 25-42, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31608458

RESUMO

The extracellular matrix (ECM) of bone and cartilage presents stem cells with a dynamic and complex array of biochemical and biomechanical signals that regulate proliferation and differentiation into bone and cartilage tissue-producing cells. Due to the multitude of signals present in this ECM, it is challenging to develop biomaterials that accurately recapitulate bone and cartilage tissues, thereby limiting the ability to present cells with multiple factors for enhanced biomaterial-induced osteogenic and chondrogenic differentiation. Conventional techniques to evaluate stem cell responses to engineered materials are laborious and time-consuming, and high-throughput screening techniques can address these limitations. Our review overviews developmental environments and signals present in bone and cartilage ECM, with a focus on applying hydrogel-based screening approaches to identify biomaterial environments that promote stem cell-mediated bone and cartilage tissue regeneration.


Assuntos
Osso e Ossos/fisiologia , Cartilagem/fisiologia , Hidrogéis/farmacologia , Regeneração/efeitos dos fármacos , Animais , Osso e Ossos/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos
4.
Int Immunopharmacol ; 77: 105928, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31711940

RESUMO

Osteoarthritis (OA), a common and severe disease, is predominantly characterized by cartilage destruction, which results in the degeneration of joint surfaces. Nowadays, it is accepted that TNFα plays a critical role in OA. Scutellarin, the main bioactive flavonoid glycoside extracted form Erigeron breviscapus, has been reported to exert positive effects on anti-inflammatory reactions. However, the effect of scutellarin in OA is still unknown. In this study, we isolated and cultured primary murine chondrocytes, stimulating TNF-α, in the presence or absence of scutellarin treatment. We found that the inflammatory response stimulated by TNF-α was significantly inhibited by the addition of scutellarin. Moreover, we established OA mouse models induced by surgery. In this mouse model, both inflammatory reaction and cartilage degeneration were markedly inhibited by oral administration of scutellarin. Furthermore, the cellular mechanism underlying the protective effect of scutellarin in OA was clearly associated with the NF-κB and PI3K/AKT signaling pathways. Collectively, this study proposes scutellarin as a potential therapeutic to treat joint degenerative diseases, including OA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Apigenina/uso terapêutico , Cartilagem/efeitos dos fármacos , Glucuronatos/uso terapêutico , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Cartilagem/metabolismo , Cartilagem/patologia , Glucuronatos/farmacologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Transdução de Sinais/efeitos dos fármacos
5.
BMC Vet Res ; 15(1): 386, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675958

RESUMO

BACKGROUND: Platelet-rich plasma (PRP) as well as other platelet-derived products have been used as a potential disease-modifying treatment for musculoskeletal diseases, such as osteoarthritis (OA). The restorative properties of such products rely mainly on the high concentrations of growth factors, demonstrating encouraging results experimentally and clinically. Yet, the autologous blood-derived nature of the PRP product lead to limitations that precludes it's widespread use. The main limitations for PRP use are; product variability, the need for minimum laboratory settings in most cases, and the need for storage at low temperatures to preserve its properties. Based on these limitations, the objective of this study was to investigate an allogeneic off-the-shelf platelet lysate (PL) in cartilage exposed to interleukin 1ß (IL-1ß). For this purpose, blood and cartilage were harvested from eight skeletally mature and healthy horses. Blood was processed into PL aliquots and divided into three groups (Frozen, Freeze-dried and Filtered freeze-dried), used in autologous and allogeneic conditions and in three different concentrations (1.5, 3 and 6-fold). Different PL preparations were then applied in cartilage culture with interleukin-1 beta and cultured for 10 days. Cartilage and media samples were collected and analyzed for total GAG and 35SO4-labeled GAG content. RESULTS: No significant differences between the controls and PL groups in cartilage and media were demonstrated. The effects of PL on cartilage matrix were concentration dependent and intermediate concentrations (3-fold) in PL showed increased 35SO4-labelled GAG in cartilage. CONCLUSION: In conclusion, the allogeneic freeze-dried PL presented equivalent effects compared to frozen autologous PL. Intermediate platelet concentration on average demonstrated improved results, demonstrating less GAG loss compared to other concentrations.


Assuntos
Plaquetas/química , Cartilagem/efeitos dos fármacos , Cavalos , Interleucina-1beta/farmacologia , Animais , Liofilização , Glicosaminoglicanos/metabolismo , Plasma Rico em Plaquetas , Técnicas de Cultura de Tecidos/veterinária
6.
Biomed Res Int ; 2019: 6508094, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737672

RESUMO

In cartilage tissue engineering, the target cells' functional performance depends on the biomaterials. However, it is difficult to develop an appropriate scaffold to differentiate mouse adipose-derived stem cells (mADSCs) into chondrocyte despite an increasing number of studies on biological scaffold materials. The purpose of this study was to create a novel scaffold for mADSC culture and chondrogenic differentiation with a new series of microgels based on polyethyleneimine (PEI), polyethylene glycol (PEG), and poly (L-lactic acid) (PLLA) and able to resist swelling with changes in temperature, pH, and polymer concentration. The biocompatibility and ability of the nonswelling microgels were then examined and served as scaffolds for cell culture and for cartilage differentiation. The results show that the new microgels are a novel biomaterial that both retains its nonswelling properties under various conditions and facilitates important scaffold functions such as cell adhesion, proliferation, and cartilage induction.


Assuntos
Adiposidade/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Microgéis/administração & dosagem , Células-Tronco/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Camundongos , Microgéis/química , Poliésteres/química , Polietilenoglicóis/química , Polietilenoimina/química , Engenharia Tecidual/métodos , Tecidos Suporte/química
7.
Med Sci Monit ; 25: 7488-7498, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587011

RESUMO

BACKGROUND Osteoarthritis (OA) is a joint disease characterized by articular cartilage degeneration and inflammation. We have previously clarified that a xanthan gum (XG) preparation exerts ameliorating effect on a rabbit OA model by regulating matrix metalloproteinase (MMP)-1 and MMP-3, which are critical proteins in the Wnt3a/ß-catenin pathway. Thus, it is reasonable to predict that the Wnt3a/ß-catenin pathway is involved in the treatment of OA with XG. MATERIAL AND METHODS The effect of XG in OA model animals were observed by hematoxylin and eosin staining (HE), Safranin O staining, and Fast Green staining. Articular cartilage degradation on the medial plateau sides was quantified using the modified Pritzker OARSI score. The levels of IL-6, TNF-alpha, and IL-1ß in synovial fluid were determined with ELISA. The protective effect of XG in rat chondrocytes was assessed by CCK8 assay. Moreover, activation of the Wnt3a/ß-catenin pathway and the expression of MMP13, ADAMTS5, aggrecan, and collagen II under the influence of XG was measured by Western blot and qRT-PCR. RESULTS Our results showed that XG reduced the OARSI score and the concentration of inflammatory cytokines in OA after intra-articular injection. XG acted on Wnt3a/ß-catenin in ATDC5 cells in a dose-dependent manner and exhibited a protective effect. XG also decreased the expression of MMP13 and ADAMTS5 and rescued the inhibition of aggrecan and collagen II expression in SNP-stimulated chondrocytes. CONCLUSIONS These results indicate that the effects of XG are related to the Wnt3a/ß-catenin pathway and XG suppresses matrix degradation by inhibiting the expression of MMPs and ADAMTS and promotes aggrecan and collagen II content in the ECM, indicating its favorable potential for use in OA therapy.


Assuntos
Osteoartrite/tratamento farmacológico , Polissacarídeos Bacterianos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Proteína ADAMTS5/metabolismo , Animais , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Cartilagem/patologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Linhagem Celular , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Modelos Animais de Doenças , Inflamação/metabolismo , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Coelhos , Ratos , Ratos Sprague-Dawley , Líquido Sinovial/efeitos dos fármacos , Líquido Sinovial/metabolismo , Proteína Wnt3A/metabolismo , beta Catenina/metabolismo
8.
Pharmacology ; 104(5-6): 216-225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31514188

RESUMO

The present study evaluated the protective effects of pseurotin A against inflammation and the destruction of cartilage in a rat model of rheumatoid arthritis (RA). RA was induced by intradermal injections of Freund's complete adjuvant (1 mg/mL), and the treatment with pseurotin A (50 and 100 mg/kg, p.o.) was administered over 1 week. The effects of pseurotin A were assessed by estimating hind paw volume (HPV) and determining the levels of inflammatory mediators in the serum and synovial fluid of collagen-induced arthritis (CIA)-induced RA rats. Western blot and histopathological assays were performed to assess changes in synovial tissues. Additionally, in vitro analyses of receptor activator of nuclear factor-kappa-Β ligand (RANKL)-stimulated RAW264.7 cells treated with pseurotin A at different concentrations (1, 10, and 100 µg/mL) were conducted to assess the effects of pseurotin A on apoptosis ratio, real-time polymerase chain reaction data, and tartrate-resistant acid phosphatase staining. Compared to the RA group, treatment with pseurotin A significantly decreased HPV and reduced the levels of inflammatory mediators in the synovial fluid and blood. Additionally, pseurotin A ameliorated the protein expressions of osteoprotegerin, nuclear factor of activated T-cells, nuclear factor-kappa beta (NF-κB), IκBα, extracellular signal regulated kinase, and P38 as well as histopathological changes in the synovial tissue of CIA-induced RA rats. The in vitro findings revealed that pseurotin A treatment did not alter the apoptosis ratio in RANKL-stimulated RAW264.7 cells but significantly reduced the mRNA expressions of calcitonin receptor, NF-κB, and matrix metallopeptidase-9. The present findings suggest that pseurotin A ameliorated the differentiation of osteoclasts and the destruction of cartilage in RA rats via regulation of the mitogen-activated protein kinase/RANKL/NF-kB pathway.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Pirrolidinonas/uso terapêutico , Animais , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Experimental/prevenção & controle , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Diferenciação Celular/efeitos dos fármacos , Citocinas/imunologia , Dinoprostona/imunologia , Modelos Animais de Doenças , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/imunologia , Osteoclastos/efeitos dos fármacos , Osteoprotegerina/imunologia , Substâncias Protetoras/farmacologia , Pirrolidinonas/farmacologia , Ligante RANK/imunologia , Células RAW 264.7 , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
9.
Inflammation ; 42(6): 2278-2285, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512108

RESUMO

Osteoarthritis (OA) is a common cause of joint pain and physical disability in the elderly. It is highly associated with local inflammatory reactions and cartilage degradation. Isorhapontigenin (ISO), a natural compound existing in various plants, has shown prominent anti-inflammatory and anti-oxidative properties in several inflammatory diseases. However, the effects of ISO on OA remain to be elucidated. Here, we investigated the effects of ISO on interleukin-1ß (IL-1ß)-treated rat chondrocytes and cartilage explants. Our results revealed that ISO could suppress the IL-1ß-induced elevated levels of nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX2). Besides, ISO could also inhibit the IL-1ß-induced up-regulation of cartilage matrix catabolic enzymes such as matrix metalloproteinases (MMPs) and aggrecanase-2 (ADAMTS5). Moreover, the IL-1ß-induced downregulation of collagen II and aggrecan could be reversed by ISO. Furthermore, ISO prevented rat cartilage explant damage induced by IL-1ß. Mechanistically, ISO worked partly by suppressing mitogen-activated protein kinase (MAPK)-associated ERK and p38 pathways. Taken together, our study indicated the anti-inflammatory potential of ISO on IL-1ß-treated rat chondrocytes, providing a new idea for OA treatment.


Assuntos
Cartilagem/patologia , Condrócitos/patologia , Inflamação/tratamento farmacológico , Estilbenos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Cartilagem/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Inflamação/induzido quimicamente , Interleucina-1beta/farmacologia , Metaloproteinases da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Osteoartrite/tratamento farmacológico , Ratos
10.
BMC Complement Altern Med ; 19(1): 252, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506082

RESUMO

BACKGROUND: Turmeric is commonly used as a dietary treatment for inflammation, but few studies have evaluated the direct effect of turmeric on cartilage. The purpose of this study was to characterize cartilage explants' inflammatory responses to lipopolysaccharide in the presence of a simulated biological extract of turmeric. METHODS: Turmeric was incubated in simulated gastric and intestinal fluid, followed by inclusion of liver microsomes and NADPH. The resulting extract (TURsim) was used to condition cartilage explants in the presence or absence of lipopolysaccharide. Explants were cultured for 96 h (h); the first 24 h in basal tissue culture media and the remaining 72 h in basal tissue culture media containing TURsim (0, 3, 9 or 15 µg/mL). Lipopolysaccharide (0 or 5 µg/mL) was added for the final 48 H. media samples were collected immediately prior to lipopolysaccharide exposure (0 h) and then at 24 and 48 h after, and analyzed for prostaglandin E2 (PGE2), glycosaminoglycan (GAG), and nitric oxide (NO). Explants were stained with calcein-AM for an estimate of live cells. Data were analyzed using a 2-way repeated measures (GAG, PGE2, NO) or 1-way ANOVA without repeated measures (viability). Significance accepted at p < 0.05. RESULTS: TURsim significantly reduced PGE2, NO and GAG, and calcein fluorescence was reduced. CONCLUSIONS: These data contribute to the growing body of evidence for the utility of turmeric as an intervention for cartilage inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Cartilagem/efeitos dos fármacos , Curcuma/química , Extratos Vegetais/farmacologia , Animais , Cartilagem/imunologia , Dinoprostona/imunologia , Glicosaminoglicanos/imunologia , Técnicas In Vitro , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/imunologia , Masculino , Óxido Nítrico/imunologia , Ratos , Suínos
11.
PLoS One ; 14(9): e0218229, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509532

RESUMO

ASB20123, a C-type natriuretic peptide/ghrelin chimeric peptide, was designed as a novel peptide and demonstrated full agonistic activity for natriuretic-peptide receptor B and a significantly longer half-life in plasma compared with the native peptide. We researched the toxicological profile of ASB20123, the correlation between the morphological change of the epiphyseal plate and bone and cartilage toxicity, and biomarkers to detect the toxicity. ASB20123 was systemically administered to male and female rats at daily dose levels of 0.5, 1.5, and 5.0 mg/kg/day for 4 weeks. In this study, toxicity was observed as changes related to bone and cartilage tissues, and no other toxicological changes were observed in all animals. Next, ASB20123 was administered to 12-month-old rats with a little epiphyseal plate. The toxic changes related to bone and cartilage tissues were not observed in any animal with a closed epiphyseal plate, indicating that the toxic changes were triggered by the growth-accelerating effect on the bone and cartilage. Furthermore, we searched for the biomarker related to the bone and cartilage toxicity using rats treated with ASB20123 at doses of 0.005, 0.05, 0.5, and 5.0 mg/kg/day for 4 weeks. A close correlation between necrosis/fibrosis in the epiphysis and metaphysis and thickness of the epiphyseal plate in the femur was confirmed in this study. A decrease in the bone mineral density (BMD) of the femur also was associated with the appearance of bone toxicity. These results indicated that the toxicity of ASB20123 was limited to bone- and cartilage-specific changes, and these changes were triggered by an excessive growth accelerating effect. Furthermore, our data suggested that the thickness of the epiphyseal plate and BMD could be reliable biomarkers to predict bone toxicity.


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Peptídeo Natriurético Tipo C/farmacologia , Animais , Biomarcadores , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Cartilagem/metabolismo , Epífises/efeitos dos fármacos , Feminino , Lâmina de Crescimento/efeitos dos fármacos , Masculino , Peptídeo Natriurético Tipo C/efeitos adversos , Peptídeo Natriurético Tipo C/análogos & derivados , Ratos
12.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502578

RESUMO

Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed after treatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterally ovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX+OA control, OVX+OA + diclofenac (5 mg/kg) (positive control), OVX+OA + LP leaf extract (150 and 300 mg/kg) and healthy sham control. After 8 weeks' treatment, their conditions were evaluated via serum biomarkers, knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilage erosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenac and the non-treated OA. The cartilage catabolic markers' (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa, CASP3 and HIF-2 alpha) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased by LP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilage protective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondral bone restoration. The cartilage ER alpha over-expression showed a strong positive correlation with MMP-13, COL10 alpha1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.


Assuntos
Envelhecimento/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Osteoartrite/tratamento farmacológico , Extratos Vegetais/farmacologia , Primulaceae/química , Envelhecimento/genética , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Diclofenaco/farmacologia , Modelos Animais de Doenças , Flavonoides/farmacologia , Ácido Gálico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Iodoacetatos/farmacologia , Metaloproteinase 13 da Matriz/genética , Metabolismo/efeitos dos fármacos , Osteoartrite/genética , Osteoartrite/patologia , Ovariectomia , Extratos Vegetais/química , Ratos
13.
Mater Sci Eng C Mater Biol Appl ; 104: 109927, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500038

RESUMO

Tissue engineering with scaffolds provides novel prospects for bone/cartilage damage healing. Previous studies mainly focus on the development of physical/chemical property of scaffold and their efficiency on tissue regeneration. The biocompatibility and biodegradation of scaffold have been questioned with their rapidly increased application, since the ultimate clinical application requires biological safety and efficiency of biomaterials. After scaffolds are implanted in living organisms, excessive inflammatory response and foreign body reaction may compromise tissue healing outcomes, or eventually lead to the failure of regeneration. Further, scaffolds degradation and degraded derivatives may elicit immunogenic reaction, cause environmental change, influence encapsulated drug/growth factor release and cellular activity. Hence, the understanding of the degradation characteristics of various biomaterials is required as well. Non-invasive monitoring the fate of scaffolds inside the body needs to be explored for temporally and longitudinally optical observation. The review mainly aims to provide a retrospective summary and discussion of the biocompatibility, immune response and fate of scaffold in cartilage/bone tissue engineering. The continuing development of sophisticated biocompatible and biomimetic scaffolds will eventually lead to clinical application which can improve the quality of patients' care and life.


Assuntos
Osso e Ossos/imunologia , Cartilagem/imunologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/farmacologia , Osso e Ossos/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Humanos , Sistema Imunitário/fisiologia
14.
Med Sci Monit ; 25: 6649-6659, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31484919

RESUMO

BACKGROUND Chondrocyte dysfunction and apoptosis are 2 major features during the progression of osteoarthritis. Catalpol, an iridoid glycoside isolated from the root of Rehmannia, is a valuable medication with anti-inflammatory, anti-oxidative, and anti-apoptotic effects in various diseases. However, whether catalpol protects against osteoarthritis has not been investigated. MATERIAL AND METHODS To assess the role of catalpol in osteoarthritis and the potential mechanism of action, chondrocytes were treated with interleukin (IL)-1ß and various concentrations of catalpol. Catabolic metabolism, apoptotic level and relative signaling pathway were measured by western blot, real-time polymerase chain reaction and immunofluorescence staining. Meanwhile, we assess the cartilage degeneration in an experimental rat model using Safranin O fast green staining and cartilage was graded according to the Osteoarthritis Research Society International (OARSI) system. RESULTS The results showed that catalpol prevented chondrocyte apoptotic level triggered by IL-1ß, suppressed the release of catabolic enzymes, and inhibited the degradation of extracellular matrix induced by IL-1ß. Catalpol also inhibited the nuclear factor kappa B (NF-kappaB) pathway, reduced the production of inflammatory cytokines (IL-6, tumor necrosis factor-alpha) in IL-1ß-treated chondrocytes, and partially reversed cartilage degeneration in the knee joint in animal model of osteoarthritis. CONCLUSIONS Our work suggested that catalpol treatment attenuates IL-1ß-induced inflammatory response and catabolism in rat chondrocytes by inhibiting the NF-kappaB pathway, suggesting the therapeutic potential of catalpol for the treatment of osteoarthritis.


Assuntos
Apoptose/efeitos dos fármacos , Cartilagem/patologia , Condrócitos/patologia , Matriz Extracelular/metabolismo , Inflamação/patologia , Interleucina-1beta/farmacologia , Glucosídeos Iridoides/farmacologia , Proteínas ADAMTS/metabolismo , Animais , Cartilagem/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Mediadores da Inflamação/metabolismo , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , NF-kappa B/metabolismo , Osteoartrite/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Int J Biol Macromol ; 139: 1168-1181, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31419553

RESUMO

Novel injectable thermosensitive PNIPAM/hyaluronic acid hydrogels containing various amounts of chitosan-g-acrylic acid coated PLGA (ACH-PLGA) micro/nanoparticles were synthesized and designed to facilitate the regeneration of cartilage tissue. The ACH-PLGA particles were used in the hydrogels to play a triple role: first, the allyl groups on the chitosan-g-acrylic acid shell act as crosslinkers for PNIPAM and improved the mechanical properties of the hydrogel to mimic the natural cartilage tissue. Second, PLGA core acts as a carrier for the controlled release of chondrogenic small molecule melatonin. Third, they could reduce the syneresis of the thermosensitive hydrogel during gelation. The optimum hydrogel with the minimum syneresis and the maximum compression modulus was chosen for further evaluations. This hydrogel showed a great integration with the natural cartilage during the adhesion test, and also, presented an interconnected porous structure in scanning electron microscopy images. Eventually, to evaluate the cytotoxicity, mesenchymal stem cells were encapsulated inside the hydrogel. MTT and Live/Dead assay showed that the hydrogel improved the cells growth and proliferation as compared to the tissue culture polystyrene. Histological study of glycosaminoglycan (GAG) showed that melatonin treatment has the ability to increase the GAG synthesis. Overall, due to the improved mechanical properties, low syneresis, the ability of sustained drug release and also high bioactivity, this injectable hydrogel is a promising material system for cartilage tissue engineering.


Assuntos
Resinas Acrílicas/química , Cartilagem/citologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ácido Hialurônico/química , Hidrogéis/farmacologia , Engenharia Tecidual , Cartilagem/efeitos dos fármacos , Técnicas de Química Sintética , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Hidrogéis/química , Injeções , Melatonina/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Microesferas , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tecidos Suporte/química
16.
Indian J Med Res ; 149(5): 641-649, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31417032

RESUMO

Background & objectives: Seeding density is one of the major parameters affecting the quality of tissue-engineered cartilage. The objective of this study was to evaluate different seeding densities of osteoarthritis chondrocytes (OACs) to obtain the highest quality cartilage. Methods: The OACs were expanded from passage 0 (P0) to P3, and cells in each passage were analyzed for gross morphology, growth rate, RNA expression and immunochemistry (IHC). The harvested OACs were assigned into two groups: low (1×10[7] cells/ml) and high (3×10[7] cells/ml) cell density. Three-dimensional (3D) constructs for each group were created using polymerised fibrin and cultured for 7, 14 and 21 days in vitro using chondrocyte growth medium. OAC constructs were analyzed with gross assessments and microscopic evaluation using standard histology, IHC and immunofluorescence staining, in addition to gene expression and biochemical analyses to evaluate tissue development. Results: Constructs with a high seeding density of 3×10[7] cells/ml were associated with better quality cartilage-like tissue than those seeded with 1×10[7] cells/ml based on overall tissue formation, cell association and extracellular matrix distribution. The chondrogenic properties of the constructs were further confirmed by the expression of genes encoding aggrecan core protein and collagen type II. Interpretation & conclusions: Our results confirmed that cell density was a significant factor affecting cell behaviour and aggregate production, and this was important for establishing good quality cartilage.


Assuntos
Cartilagem/crescimento & desenvolvimento , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Osteoartrite/terapia , Cartilagem/efeitos dos fármacos , Cartilagem Articular , Técnicas de Cultura de Células/métodos , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Fibrina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Osteoartrite/patologia , Osteogênese/efeitos dos fármacos , RNA/genética
17.
Colloids Surf B Biointerfaces ; 183: 110403, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400614

RESUMO

Efforts on bioengineering are directed towards the construction of biocompatible scaffolds and the determination of the most favorable microenvironment, which will better support cell proliferation and differentiation. Perfusion bioreactors are attracting growing attention as an effective, modern tool in tissue engineering. A natural biomaterial extensively used in regenerative medicine with outstanding biocompatibility, biodegradability and non-toxic characteristics, is collagen, a structural protein with undisputed beneficial characteristics. This is a study designed according to the above considerations. 3D printed polycaprolactone (PCL) scaffolds with rectangular pores were coated with collagen either as a coating on the scaffold's trabeculae, or as a gel-cell solution penetrating scaffolds' pores. We employed histological, molecular and imaging techniques to analyze colonization, proliferation and chondrogenic differentiation of Adipose Derived Mesenchymal Stem Cells (ADMSCs). Two different differentiation culture media were employed to test chondrogenic differentiation on gelated and non gelated PCL scaffolds in static and in perfusion bioreactors dynamic culture conditions. In dynamic culture, non gelated scaffolds combined with our in house TGF-ß2 based medium, augmented chondrogenic differentiation performance, which overall was significantly less favorable compared to StemPro™ propriety medium. The beneficial mechanical stimulus of dynamic culture, appears to outgrow the disadvantage of the "weaker" TGF-ß2 medium used for chondrogenic differentiation. Even though cells in static culture grew well on the scaffold, there was limited penetration inside the construct, so the purpose of the 3D culture was not fully served. In contrast dynamic culture achieved better penetration and uniform distribution of the cells within the scaffold.


Assuntos
Cartilagem/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Colágeno/farmacologia , Poliésteres/farmacologia , Engenharia Tecidual/métodos , Tecidos Suporte , Agrecanas/genética , Agrecanas/metabolismo , Materiais Biocompatíveis , Biomarcadores/metabolismo , Reatores Biológicos , Cartilagem/citologia , Cartilagem/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrogênese/genética , Colágeno/química , Meios de Cultura/química , Meios de Cultura/farmacologia , Expressão Gênica , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Poliésteres/química , Porosidade , Cultura Primária de Células , Impressão Tridimensional , Regeneração/genética , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Propriedades de Superfície
18.
Cells ; 8(8)2019 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382623

RESUMO

One option to fight joint degradation and inflammation in osteoarthritis is the injection of activated blood products into the synovial space. It has been demonstrated that hyperacute serum is the most proliferative among plasma products, so we investigated how the cytokine milieu of osteoarthritic knee joint reacts to hyperacute serum treatment in vitro. Cartilage, subchondral bone, and synovial membrane explanted from osteoarthritic knees were stimulated by interleukin-1 beta (IL-1ß) and the concentration of 39 biomarkers was measured in the co-culture supernatant after hyperacute serum treatment. The IL-1ß stimulation triggered a strong inflammatory response and enhanced the concentrations of matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13), while hyperacute serum treatment reduced inflammation by decreasing the concentrations of IL-1ß, tumor necrosis factor alpha (TNF-α), interleukin-6 receptor alpha (IL-6Rα), and by increasing the level of interleukin-1 antagonist (IL-1RA) Cell viability increased by day 5 in the presence of hyperacute serum. The level of MMPs-1, 2, and 9 were higher on day 3, but did not increase further until day 5. The concentrations of collagen 1 alpha 1 (COL1A1) and osteonectin were increased and receptor activator of nuclear factor kappa-B ligand (RANKL) was reduced in response to hyperacute serum. We concluded that hyperacute serum treatment induces cell proliferation of osteoarthritic joint tissues and affects the cytokine milieu towards a less inflamed state.


Assuntos
Citocinas/metabolismo , Interleucina-1beta/farmacologia , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Osteoartrite do Joelho/terapia , Adulto , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Técnicas de Cocultura , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Membrana Sinovial/efeitos dos fármacos , Técnicas de Cultura de Tecidos , Adulto Jovem
19.
Gene ; 712: 143959, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278964

RESUMO

Blockade of Hedgehog signaling can prevent osteoarthritis (OA) syndromes. However, the amelioration of related inflammation condition is limited. The purpose of this study was to observe the effect of combined use of Hedgehog signaling inhibitor GANT-61 and common clinical anti-inflammatory drug indomethacin on cartilage injury and inflammation in experimental OA mice. We found that GANT-61 and indomethacin synergistically attenuate cartilage damage and serum levels of inflammatory cytokines TNF-α, IL-2 and IL-6 in OA mice. Moreover, in vitro treatment of GANT-61 and indomethacin synergistically reduced the mRNA expression of TNF-α, IL-2 and IL-6 in lipopolysaccharide (LPS)-stimulated C28/I2 chondrocytes. Mechasnistic studies showed that GANT-61 and indomethacin synergistically attenuate the expressions of cell pyroptosis-related genes caspase-1, IL-1ß and IL-18 at mRNA and protein level. To conclude, our study showed that GANT-61 and indomethacin had a synergistically ameliorating effect on osteoarthritis by mediating chondrocytes pyroptosis.


Assuntos
Cartilagem/efeitos dos fármacos , Condrócitos/citologia , Proteínas Hedgehog/antagonistas & inibidores , Indometacina/farmacologia , Osteoartrite/tratamento farmacológico , Piridinas/administração & dosagem , Pirimidinas/administração & dosagem , Animais , Anti-Inflamatórios/farmacologia , Cartilagem/patologia , Caspase 1/metabolismo , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piroptose , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
20.
Biomed Res Int ; 2019: 5141204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346519

RESUMO

Patients with bone and cartilage defects due to infection, tumors, and trauma are quite common. Repairing bone and cartilage defects is thus a major problem for clinicians. Autologous and artificial bone transplantations are associated with many challenges, such as limited materials and immune rejection. Bone and cartilage regeneration has become a popular research topic. Inorganic polyphosphate (polyP) is a widely occurring biopolymer with high-energy phosphoanhydride bonds that exists in organisms from bacteria to mammals. Much data indicate that polyP acts as a regulator of gene expression in bone and cartilage tissues and exerts morphogenetic effects on cells involved in bone and cartilage formation. Exposure of these cells to polyP leads to the increase of cytokines that promote the differentiation of mesenchymal stem cells into osteoblasts, accelerates the osteoblast mineralization process, and inhibits the differentiation of osteoclast precursors to functionally active osteoclasts. PolyP-based materials have been widely reported in in vivo and in vitro studies. This paper reviews the current cellular mechanisms and material applications of polyP in bone and cartilage regeneration.


Assuntos
Doenças Ósseas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Polifosfatos/uso terapêutico , Doenças Ósseas/patologia , Cartilagem/crescimento & desenvolvimento , Cartilagem/patologia , Diferenciação Celular/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Humanos , Transplante de Células-Tronco Mesenquimais , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Tecidos Suporte/química
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