Assuntos
Melanoma , Osteopontina , Humanos , Melanoma/genética , Melanoma/diagnóstico , Osteopontina/genética , Osteopontina/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Processamento Alternativo , Feminino , MasculinoRESUMO
The present study aimed to evaluate the effect of photobiomodulation therapy (PBM) on different stages of osteogenesis in vitro. For this, osteoblastic-like cells (Saos-2 cell lineage) were irradiated in two different periods: during the Proliferation phase (PP; from the second to the fourth day) and during the Differentiation phase (DP; from the seventh to the ninth day). The energy density used in the study was 1.5 J/ cm2. The following parameters were evaluated: 1) quantification of collagen type 1 (COL 1), osteopontin (OPN), and bone morphogenetic protein 2 (BMP-2); 2) quantification of alkaline phosphatase (ALP) activity; and 3) quantification of extracellular matrix (ECM) mineralization. Non-irradiated cultures were used as controls. The data were analyzed using the Student's t-test or one-way ANOVA, considering a significance level of 5%. The results indicated that COL 1 and BMP-2 quantification was higher in Saos-2 irradiated during the DP in relation to the control group at day 10 (p < 0.05). No differences were observed for other comparisons at this time point (p > 0.05). OPN expression was greater in PP compared with the other experimental groups at day 10 (p < 0.05). Irradiation did not affect ALP activity in Saos-2 regardless of the exposure phase and the time point evaluated (p > 0.05). At day 14, ECM mineralization was higher in Saos-2 cultures irradiated during the DP in relation to the PP (p < 0.05). In conclusion, the results suggested that the effects of PBM on osteoblastic cells may be influenced by the stage of cell differentiation.
Assuntos
Fosfatase Alcalina , Proteína Morfogenética Óssea 2 , Diferenciação Celular , Proliferação de Células , Colágeno Tipo I , Terapia com Luz de Baixa Intensidade , Osteoblastos , Osteogênese , Osteopontina , Osteogênese/efeitos da radiação , Humanos , Proteína Morfogenética Óssea 2/metabolismo , Fosfatase Alcalina/metabolismo , Osteopontina/metabolismo , Diferenciação Celular/efeitos da radiação , Colágeno Tipo I/metabolismo , Osteoblastos/efeitos da radiação , Osteoblastos/citologia , Osteoblastos/metabolismo , Proliferação de Células/efeitos da radiação , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos da radiaçãoRESUMO
PURPOSE: This study aimed to verify whether there is a difference in biomarker levels in the gingival crevicular fluid between premenopausal and postmenopausal women undergoing orthodontic treatment. METHODS: As eligibility criteria, prospective or retrospective observational studies evaluating women undergoing orthodontic treatment (P), comparing postmenopausal (E) and premenopausal (C) women, and analyzing differences in gingival crevicular fluid biomarkers (O) were included. An electronic search was conducted in seven databases (PubMed, Scopus, Web of Science, LILACS, The Cochrane Library, Embase, and EBSCO: Dentistry & Oral Science) and one grey literature source (Google Scholar). All databases were searched from September 2022 to March 2023. After duplicate exclusion and data extraction, the Newcastle-Ottawa scale was applied to assess the quality and risk of bias, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to verify the certainty of evidence. RESULTS: Three case-control studies that analyzed receptor activator of nuclear factor kappaB ligand (RANKL), osteopontin (OPN), and interleukin (IL)-17A levels were included. One study reported a significant difference for RANKL and another for OPN levels. A third study reported that there was a higher expression of IL17A in the postmenopausal group. However, the small number of articles limits our systematic review. The heterogeneity and imprecision in the study results cast doubt on the findings' internal validity. CONCLUSION: The studies reported alterations in biomarker levels but differed in their conclusions. Therefore, further studies must include other types of bone and inflammatory biomarkers in female patients who are pre- or postmenopausal and undergoing orthodontic treatment. REGISTRATION: The review was registered at the Open Science Framework ( https://doi.org/10.17605/OSF.IO/Q9YZ8 ).
Assuntos
Biomarcadores , Líquido do Sulco Gengival , Osteopontina , Pós-Menopausa , Humanos , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/metabolismo , Feminino , Biomarcadores/análise , Biomarcadores/metabolismo , Osteopontina/análise , Osteopontina/metabolismo , Pré-Menopausa/metabolismo , Ligante RANK/análise , Ligante RANK/metabolismo , Interleucina-17/análise , Interleucina-17/metabolismo , Ortodontia CorretivaRESUMO
Kisspeptin (Kp-10) is a neuropeptide that binds to GPR54 receptors, exerting several functions mainly in the nervous and reproductive systems of the body. However, its effects and mechanisms of action on the skeletal system remain poorly understood. This study evaluated the effects of different concentrations of Kp-10 on in vitro osteogenic differentiation of multipotent mesenchymal stromal cells (MSCs) extracted from the bone marrow (BM) of adult Wistar rats. Two-month-old female rats were euthanized to extract BM from long bones to obtain MSCs. Four experimental groups were established in vitro: a control and Kp-10 at concentrations of 0.01, 0.05 and, 0.1 µg/mL. After induction of osteogenic differentiation, cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide (MTT) assay, alkaline phosphatase activity, collagen synthesis, percentage of area covered by MSCs/field and mineralized nodules/field, and immunocytochemistry of the GPR54 receptor tests. Furthermore, evaluation of gene transcripts for type I collagen, Runx-2, Bmp-2, bone sialoprotein, osteocalcin and osteopontin was performed using real-time RT-qPCR. It was observed that MSCs expressed GPR54 receptor to which Kp-10 binds during osteogenic differentiation, promoting a negative effect on osteogenic differentiation. This effect was observed at all the Kp-10 concentrations in a concentration-dependent manner, characterized by a decrease in the activity of alkaline phosphatase, collagen synthesis, mineralized nodules, and decreased expression of gene transcripts for type I collagen, osteocalcin, osteopontin, and Runx-2. Thus, Kp-10 inhibits in vitro osteogenic differentiation of MSCs extracted from the BM of adult Wistar rats.
Assuntos
Kisspeptinas , Células-Tronco Mesenquimais , Osteogênese , Animais , Feminino , Ratos , Fosfatase Alcalina/metabolismo , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Diferenciação Celular , Células Cultivadas , Colágeno Tipo I/metabolismo , Kisspeptinas/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteocalcina/genética , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Osteopontina/metabolismo , Osteopontina/farmacologia , Ratos WistarRESUMO
The increase in life expectancy has led to a higher incidence of osteoporosis, characterized by an imbalance in bone remodeling. Several drugs are used for its treatment, but most promote undesirable side effects. The present investigation evaluated the effects of two low concentrations of grape seed extract (GSE) rich in proanthocyanidins on MC3T3-E1 osteoblastic cells. The cells were cultured in an osteogenic medium and divided into control (C), 0.1 µg/mL GSE (GSE0.1), and 1.0 µg/mL GSE (GSE1.0) groups to evaluate cell morphology, adhesion, and proliferation, in situ alkaline phosphatase (ALP) detection, mineralization and immunolocalization of osteopontin (OPN). The data obtained were analyzed by statistical tests for a significance of 5%. Cell morphology was maintained with both GSE concentrations, whereas cell adhesion significantly increased within three days in all groups. Cell proliferation increased significantly at seven days of culture, followed by a significant decrease in all experimental periods, with no statistical difference among them. In situ detection of ALP and mineralization increased with time, but within each period, no statistical differences among groups were observed. The expression of osteopontin was distributed regularly with more intensity after 24 hours in the GSE0.1 group. After three days, OPN expression was more intense in the control group, followed by GSE0.1 and GSE1.0 groups. Data obtained suggest that low concentrations of GSE do not affect the morphology and may stimulate the functional activity of osteoblastic cells.
Assuntos
Extrato de Sementes de Uva , Extrato de Sementes de Uva/farmacologia , Osteopontina/metabolismo , Adesão Celular , Osteogênese , Proliferação de Células , Osteoblastos , Diferenciação Celular , Fosfatase Alcalina/metabolismoRESUMO
Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN's multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.
Assuntos
Artrite Reumatoide , Osteoartrite , Osteopontina , Animais , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteopontina/metabolismo , Membrana Sinovial/metabolismo , HumanosRESUMO
Classically, osteopontin (OPN) has been described as a secreted glycophosprotein. Indeed, most data concerning its physiological and pathological roles are mainly related to the secreted OPN (sOPN). However, there are several instances in which intracellular OPN (iOPN) has been described, presenting some specific roles in distinct experimental models, such as in the immune system, cancer cells, and neurological disorders. We herein aimed to highlight and discuss some of these secreted and intracellular roles of OPN and their putative clinical and biological impacts. Moreover, by consolidating data from the OPN protein database, we also analyzed the occurrence of signal peptide (SP) sequences and putative subcellular localization, especially concerning currently known OPN splicing variants (OPN-SV). Comprehending the roles of OPN in its distinct cellular and tissue environments may provide data regarding the additional applications of this protein as biomarkers and targets for therapeutic purposes, besides further describing its pleiotropic roles.
Assuntos
Osteopontina , Splicing de RNA , Osteopontina/genética , Osteopontina/metabolismoRESUMO
OBJECTIVE: Women with HIV (WWH) have heightened heart failure risk. Plasma OPN (osteopontin) is a powerful predictor of heart failure outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated heart failure risk. DESIGN: Prospective, cross-sectional. METHODS: We analyzed relationships between plasma OPN and cardiac structure/function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH). RESULTS: Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρâ=â0.51, Pâ=â0.02) and soluble interleukin 1 receptor-like 1 (ρâ=â0.45, Pâ=â0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρâ=â0.49, Pâ=â0.03) and myocardial steatosis (ρâ=â0.46, Pâ=â0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on nonclassical (CD14-CD16+) monocytes (whole group: ρâ=â0.36, Pâ=â0.04; WWH: ρâ=â0.46, Pâ=â0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH: ρâ=â0.54, Pâ=â0.01; WWOH: ρâ=â0.60, Pâ=â0.03), and in WWH, this held even after controlling for HIV-specific parameters. CONCLUSION: Among WWH, plasma OPN, a powerful predictor of heart failure outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in heart failure pathogenesis among WWH. CLINICALTRIALSGOV REGISTRATION: NCT02874703.
Assuntos
Infecções por HIV , Insuficiência Cardíaca , Humanos , Feminino , Osteopontina/metabolismo , Estudos Transversais , Estudos Prospectivos , Infecções por HIV/complicações , Fibrose , Receptores de Quimiocinas , Monócitos/metabolismoRESUMO
OBJECTIVE: The aim of this study was to evaluate the effects of caffeic acid phenethyl ester (CAPE) on osteoblast-like cell cultures (SAOS-2). METHODS: SAOS-2 were exposed to CAPE at 1 nM, 10 nM, 100 nM, 1 µM, and 10 µM. Non-exposed cultures were used as control. The following parameters were assayed: 1) cell viability at 1, 3, and 7 days; 2) alkaline phosphatase (ALP) activity at 5 and 10 days; 3) matrix mineralization at 14 days; and 4) Runt-related transcription factor 2 (RUNX2), ALP, osteopontin (SPP1), and osteocalcin (BGLAP) gene expression at 5 and 10 days. The data were analyzed by ANOVA two-way or Kruskal-Wallis (α = 5%). RESULTS: At day 1, cell viability was similar among all groups (p > 0.05). At days 3 and 7, cultures exposed to CAPE at 10 µM exhibited a significant reduction in cell viability compared with the others groups (p < 0.05). At day 5, ALP activity was similar among all experimental groups; at day 10, however, the stain intensity was higher in cultures exposed to CAPE at 100 nM and 10 nM in comparison with the other groups (p < 0.05). At days 5 and 10, RUNX2, ALP, SPP1, and BGLAP gene expression was greater in cultures exposed to CAPE in comparison with the control (p < 0.05). At day 14, matrix mineralization was similar in cultures exposed to CAPE at 1 nM and 10 nM (p > 0.05), but superior to those ones observed in the other experimental groups (p < 0.05). CONCLUSION: CAPE at low concentrations can positively module the osteogenesis in vitro.
Assuntos
Ácidos Cafeicos/farmacologia , Osteogênese/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Matriz Óssea/efeitos dos fármacos , Matriz Óssea/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Calcificação Fisiológica/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/genética , Osteopontina/genética , Osteopontina/metabolismo , Álcool Feniletílico/farmacologiaRESUMO
Glyphosate [N-(phosphonomethyl)glycine] is the active ingredient in widely used broad-spectrum herbicides. Even though the toxicity mechanism of this herbicide in vertebrates is poorly understood, evidence suggests that glyphosate is an endocrine disruptor capable of producing morphological anomalies as well as cardiotoxic and neurotoxic effects. We used the zebraï¬sh model to assess the effects of early life glyphosate exposure on the development of cartilage and bone tissues and organismal responses. We found functional alterations, including a reduction in the cardiac rate, significant changes in the spontaneous tail movement pattern, and defects in craniofacial development. These effects were concomitant with alterations in the level of the estrogen receptor alpha osteopontin and bone sialoprotein. We also found that embryos exposed to glyphosate presented spine deformities as adults. These developmental alterations are likely induced by changes in protein levels related to bone and cartilage formation.