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1.
Genes (Basel) ; 15(2)2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38397163

ABSTRACT

Extra virgin olive oil phenolic compounds have been identified as possible biostimulant agents against different pathological processes, including alterations in healing processes. However, there is little evidence on the molecular mechanisms involved in this process. The aim was to analyse the effect of hydroxytyrosol, tyrosol, and oleocanthal on fibroblast gene expression. PCR was used to determine the expression of different differentiation markers, extracellular matrix elements, and growth factors in cultured human fibroblasts CCD-1064Sk treated with different doses of hydroxytyrosol (10-5 M and 10-6 M), tyrosol (10-5 M and 10-6 M), and oleocanthal (10-6 M and 10-7 M). After 24 h of hydroxytyrosol treatment, increased expression of connective tissue growth factor, fibroblast growth factor (FGF), platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor ß1 (TGF-ß1), and their receptors was observed. Tyrosol and olecanthal modulated the expression of FGF and TGFßR1. All phytochemicals tested modified the expression of differentiation markers and extracellular matrix elements, increasing gene expression of actin, fibronectin, decorin, collagen I, and III. Phenolic compounds present in extra virgin olive could have a beneficial effect on tissue regeneration by modulating fibroblast physiology.


Subject(s)
Aldehydes , Cyclopentane Monoterpenes , Phenols , Phenylethyl Alcohol/analogs & derivatives , Plant Oils , Vascular Endothelial Growth Factor A , Humans , Olive Oil/pharmacology , Plant Oils/analysis , Biomarkers , Antigens, Differentiation , Cell Proliferation , Fibroblasts , Gene Expression
2.
Nutrients ; 15(9)2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37432217

ABSTRACT

Fibroblasts contribute to maintaining tissue integrity and homeostasis and are a key cell population in wound healing. This cell population can be stimulated by some bioactive compounds such as extra virgin olive oil (EVOO) polyphenols. The aim of this study was to determine the effects of hydroxytyrosol (htyr), tyrosol (tyr), and oleocanthal (ole) phenolic compounds present in EVOO on the proliferation, migration, cell cycle, and antigenic profile of cultured human fibroblasts. CCD-1064Sk human fibroblast cells were treated for 24 h with each polyphenol at doses ranging 10-5 to 10-9 M. Cell proliferation was evaluated using the MTT spectrophotometric technique, migration capacity by culture insert assay, and cell cycle and antigenic profile with flow cytometry. Cell proliferation was significantly increased by treatment with all compounds. The highest increases followed treatments with htyr or tyr at doses of 10-5 or 10-6 M and with ole at 10-6 and 10-7 M, and these compounds and doses were used for assays of antigenic profile, cell cycle, and migration. During the first few hours after treatment, increased fibronectin and α-actin expressions and greater cell migration were observed, with no cell cycle changes. In conclusion, these in vitro results suggest that phenolic compounds in EVOO might contribute to wound healing through action on fibroblasts related to tissue regeneration.


Subject(s)
Fibroblasts , Polyphenols , Humans , Olive Oil/pharmacology
3.
Int J Mol Sci ; 24(5)2023 Feb 21.
Article in English | MEDLINE | ID: mdl-36901687

ABSTRACT

Bone effects attributed to bisphenols (BPs) include the inhibition of growth and differentiation. This study analyzes the effect of BPA analogs (BPS, BPF, and BPAF) on the gene expression of the osteogenic markers RUNX2, osterix (OSX), bone morphogenetic protein-2 (BMP-2), BMP-7, alkaline phosphatase (ALP), collagen-1 (COL-1), and osteocalcin (OSC). Human osteoblasts were obtained by primary culture from bone chips harvested during routine dental work in healthy volunteers and were treated with BPF, BPS, or BPAF for 24 h at doses of 10-5, 10-6, and 10-7 M. Untreated cells were used as controls. Real-time PCR was used to determine the expression of the osteogenic marker genes RUNX2, OSX, BMP-2, BMP-7, ALP, COL-1, and OSC. The expression of all studied markers was inhibited in the presence of each analog; some markers (COL-1; OSC, BMP2) were inhibited at all three doses and others only at the highest doses (10-5 and 10-6 M). Results obtained for the gene expression of osteogenic markers reveal an adverse effect of BPA analogs (BPF, BPS, and BPAF) on the physiology of human osteoblasts. The impact on ALP, COL-1, and OSC synthesis and therefore on bone matrix formation and mineralization is similar to that observed after exposure to BPA. Further research is warranted to determine the possible contribution of BP exposure to the development of bone diseases such as osteoporosis.


Subject(s)
Bone Morphogenetic Protein 7 , Core Binding Factor Alpha 1 Subunit , Humans , Bone Morphogenetic Protein 7/metabolism , Core Binding Factor Alpha 1 Subunit/metabolism , Osteoblasts/metabolism , Osteogenesis , Gene Expression , Benzhydryl Compounds/pharmacology
4.
Nutrients ; 16(1)2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38201853

ABSTRACT

BACKGROUND: Pomegranate is a fruit that contains various phenolic compounds, including punicalagin and ellagic acid, which have been attributed to anti-inflammatory, antioxidant, and anticarcinogenic properties, among others. OBJECTIVE: To evaluate the effect of punicalagin and ellagic acid on the viability, migration, cell cycle, and antigenic profile of cultured human fibroblasts (CCD-1064Sk). MTT spectrophotometry was carried out to determine cell viability, cell culture inserts were used for migration trials, and flow cytometry was performed for antigenic profile and cell cycle analyses. Cells were treated with each phenolic compound for 24 h at doses of 10-5 to 10-9 M. RESULTS: Cell viability was always significantly higher in treated versus control cells except for punicalagin at 10-9 M. Doses of punicalagin and ellagic acid in subsequent assays were 10-6 M or 10-7 M, which increased the cell migration capacity and upregulated fibronectin and α-actin expression without altering the cell cycle. CONCLUSIONS: These in vitro findings indicate that punicalagin and ellagic acid promote fibroblast functions that are involved in epithelial tissue healing.


Subject(s)
Ellagic Acid , Fibroblasts , Humans , Ellagic Acid/pharmacology , Hydrolyzable Tannins/pharmacology , Cell Cycle
5.
Food Funct ; 13(22): 11410-11424, 2022 Nov 14.
Article in English | MEDLINE | ID: mdl-36282027

ABSTRACT

The olive tree and its derivatives are of great interest in the field of biomedicine due to their numerous health properties. The aim of the present study was to identify the effects of the use of olive products, extra virgin olive oil (EVOO) and products derived from its extraction, on the skin. Numerous studies have pointed out the protective effect of olive compounds on skin ageing, thanks to their role in the different mechanisms involved in the ageing process, such as reducing oxidative stress, increasing cell viability and decreasing histological alterations. With regard to their photoprotective effect, the olive tree and its fruit contain phenolic compounds which have a protective effect against radiation, such as low ultraviolet absorption and high antioxidant activity, acting as a protective factor against photocarcinogenesis. Similarly, the anti-tumour effects of olives have been studied at the level of the different compounds and extracts obtained from them, and their ability to selectively attack human melanoma cells has been observed. They have also shown antibacterial activity against microorganisms particularly implicated in skin infections, such as Escherichia coli, Candida albicans, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa and Proteus spp. Likewise, on healthy tissue, they have shown the ability to stimulate growth, migration and the expression of genes involved in cell differentiation, which favours the regeneration of skin wounds. According to the results included in this review, the olive tree and its derivatives could be useful in the treatment of many skin conditions.


Subject(s)
Olea , Humans , Olive Oil , Phenols/pharmacology , Fruit , Antioxidants/pharmacology
6.
Int J Mol Sci ; 23(10)2022 May 11.
Article in English | MEDLINE | ID: mdl-35628159

ABSTRACT

(1) Background: Bisphenol A (BPA) is an endocrine disruptor that is widely present in the environment and exerts adverse effects on various body tissues. The objective of this study was to determine its repercussions on bone tissue by examining its impact on selected functional parameters of human osteoblasts. (2) Methods: Three human osteoblast lines were treated with BPA at doses of 10-5, 10-6, or 10-7 M. At 24 h post-treatment, a dose-dependent inhibition of cell growth, alkaline phosphatase activity, and mineralization was observed. (4) Results: The expression of CD54 and CD80 antigens was increased at doses of 10-5 and 10-6 M, while the phagocytic capacity and the expression of osteogenic genes (ALP, COL-1, OSC, RUNX2, OSX, BMP-2, and BMP-7) were significantly and dose-dependently reduced in the presence of BPA. (5) Conclusions: According to these findings, BPA exerts adverse effects on osteoblasts by altering their differentiation/maturation and their proliferative and functional capacity, potentially affecting bone health. Given the widespread exposure to this contaminant, further human studies are warranted to determine the long-term risk to bone health posed by BPA.


Subject(s)
Benzhydryl Compounds , Osteoblasts , Benzhydryl Compounds/pharmacology , Humans , Osteoblasts/metabolism , Osteogenesis , Phenols/pharmacology
7.
Foods ; 10(7)2021 Jul 15.
Article in English | MEDLINE | ID: mdl-34359512

ABSTRACT

The treatment of tissue damage produced by physical, chemical, or mechanical agents involves considerable direct and indirect costs to health care systems. Wound healing involves a series of molecular and cellular events aimed at repairing the defect in tissue integrity. These events can be favored by various natural agents, including the polyphenols in extra virgin olive oil (EVOO). The objective of this study was to review data on the potential effects of different phenolic compounds that can also be found in EVOO on wound healing and closure. Results of in vitro and animal studies demonstrate that polyphenols from different plant species, also present in EVOO, participate in different aspects of wound healing, accelerating this process through their anti-inflammatory, antioxidant, and antimicrobial properties and their stimulation of angiogenic activities required for granulation tissue formation and wound re-epithelialization. These results indicate the potential usefulness of EVOO phenolic compounds for wound treatment, either alone or in combination with other therapies. Human studies are warranted to verify this proposition.

8.
J Tissue Viability ; 30(3): 372-378, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33810929

ABSTRACT

Some micronutrients of vegetable origin are considered potentially useful as wound-healing agents because they can increase fibroblast proliferation and differentiation. THE AIM OF THIS STUDY: was to evaluate the regenerative effects of selected olive oil phenolic compounds on cultured human fibroblasts and explore their antimicrobial properties. MATERIAL AND METHODS: The CCD-1064Sk fibroblast line was treated for 24 h with 10-6M luteolin, apigenin, ferulic, coumaric acid or caffeic acid, evaluating the effects on cell proliferation by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) spectrophotometric assay; the migratory capacity by the scratch assay and determining the expression of Fibroblast Growth Factor (FGF), Vascular Endothelial Growth Factor (VEGF), Transforming Growth Factor- ß1 (TGFß1), Platelet Derived Growth Factor (PDGF), and Collagen Type I (COL-I) genes by real-time polymerase chain reaction. The antimicrobial capacity of the polyphenols was evaluated by the disc diffusion method. RESULTS: All compounds except for ferulic acid significantly stimulated the proliferative capacity of fibroblasts, increasing their migration and their expression of the aforementioned genes. With respect to their antimicrobial properties, treatment with the studied compounds inhibited the growth of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Proteus spp., and Candida Albicans. CONCLUSIONS: The phenolic compounds in olive oil have a biostimulatory effect on the regeneration capacity, differentiation, and migration of fibroblasts and exert major antibacterial activity. According to the present findings, these compounds may have a strong therapeutic effect on wound recovery.


Subject(s)
Anti-Infective Agents/pharmacology , Fibroblasts/drug effects , Olive Oil/pharmacology , Regeneration/drug effects , Anti-Infective Agents/administration & dosage , Cell Proliferation/drug effects , Humans , Olive Oil/administration & dosage
9.
Int J Med Sci ; 16(12): 1534-1540, 2019.
Article in English | MEDLINE | ID: mdl-31839740

ABSTRACT

The aim of this study was to elucidate the role of fibroblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ), evaluating the effect of zoledronate, alendronate, and ibandronate on the proliferation of fibroblasts and on their expression of genes essential for fibroblast physiology. Human CCD-1064Sk epithelial fibroblast cells were incubated in culture medium with 10-5, 10-7, or 10-9 M zoledronate, alendronate, or ibandronate. The proliferative capacity of fibroblasts was determined by spectrophotometry (MTT) at 24 of culture. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of BPs at a dose of 10-9 M on the expression of FGF, CTGF, TGF-ß1, TGFßR1, TGFßR2, TGFßR3, DDR2, α-actin, fibronectin, decorin, and elastin. Fibroblasts proliferation was significantly increased at the lowest dose (10-9M) of each BP but was not affected at the higher doses (10-5 and 10-7M). The proliferation increase may be related to the rise in TGF-ß1 and TGFßR1 expression detected after the treatment of cells with 10-9M of zoledronate, alendronate, or ibandronate. However, the expression of CTGF, DDR2, α-actin, fibronectin, and decorin decreased versus controls. The results of this in vitro study indicate that a very low BP dose (10-9 M) can significantly affect the physiology of fibroblasts, increasing their proliferative capacity and modulating the expression of multiple genes involved in their growth and differentiation.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Cell Proliferation/drug effects , Diphosphonates/pharmacology , Fibroblasts/drug effects , Alendronate/pharmacology , Bisphosphonate-Associated Osteonecrosis of the Jaw/genetics , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology , Cell Differentiation/drug effects , Gene Expression Regulation/drug effects , Humans , Ibandronic Acid/pharmacology , Jaw/drug effects , Jaw/metabolism , Jaw/pathology , Osteoblasts/drug effects , Real-Time Polymerase Chain Reaction , Zoledronic Acid/pharmacology
10.
Sci Rep ; 9(1): 12037, 2019 08 19.
Article in English | MEDLINE | ID: mdl-31427686

ABSTRACT

Low-Level Laser Therapy is used as regenerative therapy in different clinical fields. This is due to its photobiomodulation effect via cell signaling on different cell populations, Including fibroblasts, cells involved in tissue regeneration and healing. The aim was to analyze the effect of 940 nm diode laser on the gene expression of different markers involved in fibroblast growth, differentiation, and migration. Real-time polymerase chain reaction (q-RT-PCR) was used to quantify the expression of fibroblast growth factor (FGF), connective tissue growth factor (CTGF), vascular-endothelial growth factor (VEGF), transforming growth factor ß1 (TGF-ß1), TGFß-receptors (TGFßR1, TGFßR2, and TGFßR3), discoidin-domain receptor-2 (DDR2), matrix metalloproteinase-2 (MMP2), α-actin, fibronectin, decorin, and elastin on human fibroblast, treated with single dose (T1) or two doses (T2) of diode laser at 0.5 Watts and 4 J/cm2. A significant increase in the expression of FGF, TGF-ß1, TGFßR1, TGFßR2, α-actin, fibronectin, decorin, DDR2 and MMP2 was observed after both treatments. A decrease was observed in expression of elastin (T1 and T2), and CTGF (T2). These changes underlie the biostimulatory effect of laser on fibroblasts, which translates into an increase in short-term proliferation and in long-term differentiation to myofibroblasts. These data support the therapeutic potential of diode laser for wound repair.


Subject(s)
Fibroblasts/metabolism , Fibroblasts/radiation effects , Gene Expression Regulation/radiation effects , Lasers, Semiconductor , Biomarkers , Cells, Cultured , Dose-Response Relationship, Radiation , Humans
11.
Nutr. hosp ; 36(4): 786-791, jul.-ago. 2019. tab
Article in Spanish | IBECS | ID: ibc-184701

ABSTRACT

Introducción: el momento en que el recién nacido recibe la primera toma no ha sido estudiado de modo explícito y se necesitan investigaciones para evaluar las medidas de apoyo a la lactancia. Nuestro objetivo fue determinar la prevalencia del inicio precoz de la lactancia materna (IPLM) y analizar su relación con distintos factores maternos y del recién nacido. Métodos: estudio descriptivo transversal realizado durante tres años en un hospital público. La base de datos utilizada para el estudio procedió de un registro clínico electrónico. Se realizó un análisis univariado descriptivo de todas las variables y se analizó la relación existente entre el IPLM con distintos parámetros maternos y del recién nacido mediante el test de Fisher. Resultados: nuestros resultados mostraron que la prevalencia de un IPLM fue de un 88,4%, de un total de 2.683 nacimientos incluidos en el estudio. Además, se encontró asociación significativa entre este IPLM y distintos factores maternos, como la paridad (p = 0,05) y las semanas de gestación (p = 0,047), excepto con la edad (p = 0,522). Igualmente, se encontró una asociación fuerte con todos los factores del niño (p = 0,000), como el peso, el color del líquido amniótico, el test de Apgar al minuto y a los cinco minutos, el tipo de reanimación que precisaba o la necesidad de ingreso en la unidad neonatal. Conclusiones: la tasa de IPLM en nuestro ámbito de estudio es alta y está influenciada por distintos factores maternos y del recién nacido


Introduction: the situation with maternal breastfeeding is difficult to describe with any certainty, given the absence of any data gathered in maternity hospitals, and the timing of its onset has not been explicitly evaluated. Further research is needed to evaluate breastfeeding support measures. The objective of the present study was to determine the prevalence of early onset of maternal breastfeeding (EOMB) and to analyze the relationship with different maternal and newborn factors. Methods: a descriptive study was performed of births in a public hospital over a three-year period. The database used for the study derived from an electronic clinical record system designed by professionals. Descriptive and univariate analyses were performed. The association of early onset of maternal breastfeeding with other parameters from mother and newborn was analyzed by the Fisher's test. Results: the prevalence of EOMB was 88.4%. A total of 2,683 births were included in the study. Significant associations were found between this EOMB and different maternal factors, such as parity (p = 0.05) and weeks of gestation (p = 0.047), but not with age (p = 0.522). A strong association was also found with all the factors of the child (p = 0.000), such as weight, color of the amniotic fluid, the Apgar test at one and five minutes, the type of resuscitation required or the need for admission in the neonatal unit. Conclusions: There has been a high rate of (EOMB) in our setting


Subject(s)
Humans , Infant, Newborn , Adult , Breast Feeding , Maternal Age , Infant Nutrition , Cross-Sectional Studies , Epidemiology, Descriptive , Apgar Score
12.
Nutr Hosp ; 36(4): 786-791, 2019 Aug 26.
Article in Spanish | MEDLINE | ID: mdl-31282172

ABSTRACT

INTRODUCTION: Introduction: the situation with maternal breastfeeding is difficult to describe with any certainty, given the absence of any data gathered in maternity hospitals, and the timing of its onset has not been explicitly evaluated. Further research is needed to evaluate breastfeeding support measures. The objective of the present study was to determine the prevalence of early onset of maternal breastfeeding (EOMB) and to analyze the relationship with different maternal and newborn factors. Methods: a descriptive study was performed of births in a public hospital over a three-year period. The database used for the study derived from an electronic clinical record system designed by professionals. Descriptive and univariate analyses were performed. The association of early onset of maternal breastfeeding with other parameters from mother and newborn was analyzed by the Fisher's test. Results: the prevalence of EOMB was 88.4%. A total of 2,683 births were included in the study. Significant associations were found between this EOMB and different maternal factors, such as parity (p = 0.05) and weeks of gestation (p = 0.047), but not with age (p = 0.522). A strong association was also found with all the factors of the child (p = 0.000), such as weight, color of the amniotic fluid, the Apgar test at one and five minutes, the type of resuscitation required or the need for admission in the neonatal unit. Conclusions: There has been a high rate of (EOMB) in our setting.


INTRODUCCIÓN: Introducción: el momento en que el recién nacido recibe la primera toma no ha sido estudiado de modo explícito y se necesitan investigaciones para evaluar las medidas de apoyo a la lactancia. Nuestro objetivo fue determinar la prevalencia del inicio precoz de la lactancia materna (IPLM) y analizar su relación con distintos factores maternos y del recién nacido. Métodos: estudio descriptivo transversal realizado durante tres años en un hospital público. La base de datos utilizada para el estudio procedió de un registro clínico electrónico. Se realizó un análisis univariado descriptivo de todas las variables y se analizó la relación existente entre el IPLM con distintos parámetros maternos y del recién nacido mediante el test de Fisher. Resultados: nuestros resultados mostraron que la prevalencia de un IPLM fue de un 88,4%, de un total de 2.683 nacimientos incluidos en el estudio. Además, se encontró asociación significativa entre este IPLM y distintos factores maternos, como la paridad (p = 0,05) y las semanas de gestación (p = 0,047), excepto con la edad (p = 0,522). Igualmente, se encontró una asociación fuerte con todos los factores del niño (p = 0,000), como el peso, el color del líquido amniótico, el test de Apgar al minuto y a los cinco minutos, el tipo de reanimación que precisaba o la necesidad de ingreso en la unidad neonatal. Conclusiones: la tasa de IPLM en nuestro ámbito de estudio es alta y está influenciada por distintos factores maternos y del recién nacido.


Subject(s)
Breast Feeding/statistics & numerical data , Adult , Age Factors , Amniotic Fluid , Analysis of Variance , Apgar Score , Birth Rate , Birth Weight , Color , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Maternal Age , Parity , Pregnancy , Time Factors
13.
Nutrients ; 11(8)2019 Jul 25.
Article in English | MEDLINE | ID: mdl-31349732

ABSTRACT

The phenolic compounds of extra-virgin olive oil can act at various levels to protect individuals against cardiovascular and neurodegenerative diseases, cancer, and osteoporosis, among others. Polyphenols in extra-virgin olive oil can stimulate the proliferation of osteoblasts, modify their antigen profile, and promote alkaline phosphatase synthesis. The objective of this work was to determine the effect of different extra-virgin olive oil phenolic compounds on the gene expression of osteoblast-related markers. The cells of the MG63 osteoblast line were cultured for 24 h with 10-6 M of the phenolic compounds ferulic acid, caffeic acid, coumaric acid, apigenin, or luteolin. The expression of studied markers was quantified using quantitative real-time polymerase chain reaction (q-RT-PCR). The expression by MG63 osteoblasts of growth and differentiation/maturation markers was modified after 24 h of treatment with 10-6 M of the phenolic compounds under study, most of which increased the gene expression of the transforming growth factor ß1 (TGF-ß1), TGF-ß receptor 1,2 and 3 (TGF-ßR1, TGF-ßR2, TGF-ßR3), bone morphogenetic protein 2 and 7 (BMP2, BMP7), run-related transcription factor 2 (RUNX-2), Alkaline phosphatase (ALP), Osteocalcin (OSC), Osterix (OSX), Collagen type I (Col-I) and osteoprotegerin (OPN). The extra-virgin olive oil phenolic compounds may have a beneficial effect on bone by modulating osteoblast physiology, which would support their protective effect against bone pathologies.


Subject(s)
Bone Density Conservation Agents/pharmacology , Olive Oil , Osteoblasts/drug effects , Osteogenesis/drug effects , Phenols/pharmacology , Adolescent , Bone Density Conservation Agents/isolation & purification , Cell Line , Gene Expression Regulation , Humans , Male , Olive Oil/chemistry , Osteoblasts/metabolism , Osteogenesis/genetics , Phenols/isolation & purification
14.
Clin Oral Investig ; 23(2): 813-820, 2019 Feb.
Article in English | MEDLINE | ID: mdl-29876664

ABSTRACT

OBJECTIVES: The objectives of this study were to analyze the effect of pH on the growth and activity of osteoclasts treated with different doses of two nitrogen-containing BPs, zoledronate and alendronate. MATERIALS AND METHODS: Murine osteoclasts cultured on dentine disks were treated with zoledronate (50 or 500 nM) or alendronate (500 or 5 µM) at two different pH values (7.4 or 7.0). Osteoclasts were counted with transmitted light microscopy, apoptosis/necrosis was studied with flow cytometry and confocal microscopy, and resorption pit number and depth were calculated using reflected light and scanning electron microscopy. RESULTS: The osteoclast count on dentine disks was significantly (p < 0.001) reduced by zoledronate or alendronate treatment at pH 7.0 in comparison to treatment with the same doses at pH 7.4 and untreated disks (controls). The percentage of apoptotic cells was significantly increased by treatment with 500 nM zoledronate or 5 µM alendronate at pH 7.0 in comparison to the same doses at pH 7.4. The number and depth of resorption pits were significantly lower in disks treated at each BP dose studied than in untreated controls at pH 7.0. CONCLUSIONS: Zoledronate and alendronate at therapeutic doses have an adverse effect on the viability and resorptive activity of osteoclasts when the local medium pH is reduced. CLINICAL RELEVANCE: These findings suggest that periodontal or peri-implant oral cavity infection may be a key trigger of the cascade of events that lead to BRONJ.


Subject(s)
Alendronate/pharmacology , Bone Density Conservation Agents/pharmacology , Osteoclasts/drug effects , Zoledronic Acid/pharmacology , Animals , Cells, Cultured , Dentin , Flow Cytometry , Hydrogen-Ion Concentration , In Vitro Techniques , Mice , Microscopy, Confocal , Microscopy, Electron, Scanning
15.
PeerJ ; 6: e5415, 2018.
Article in English | MEDLINE | ID: mdl-30128197

ABSTRACT

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used in clinical practice, which can have adverse effects on the osteoblast. The objective of this study was to determine the effect of NSAIDs on the osteoblast by analyzing the gene expression of different markers related to osteoblast maturation and function when treated in vitro with different NSAIDs. METHODS: Three human osteoblast lines from bone samples of three healthy volunteers were treated with 10 µM acetaminophen, indomethacin, ketoprofen, diclofenac, ibuprofen, ketorolac, naproxen, and piroxicam. The gene expression of different markers (run related transcription factor 2 [RUNX-2], type 1 collagen [COL-I], osterix [OSX], osteocalcin [OSC], bone morphogenetic protein 2 [BMP-2] and 7 [BMP-7], transforming growth factor ß1 [TGF-ß1], and TGFß receptors [TGFßR1, TGFßR2; TGFBR3]) were analyzed by real-time PCR at 24 h of treatment. RESULTS: Expression of RUNX-2, COL-I, OSX, was reduced by treatment with all studied NSAIDs, OSC expression was reduced by all NSAIDs except for ketoprofen, naproxen, or piroxicam. Expression of BMP-7 was reduced by all NSAIDs; BMP-2 was reduced by all except for naproxen. In general, NSAID treatment increased the expression of TGF-ß1, but not of its receptors (TGFß-R1, TGFß-R2, andTFGß-R3), which was either unchanged or reduced by the treatment. CONCLUSION: These data confirm that NSAIDs can affect osteoblast physiology, suggesting their possible impact on bone.

16.
Arch Oral Biol ; 92: 75-78, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29763781

ABSTRACT

OBJECTIVE: To determine the effect of different nonsteroidal anti-inflammatory drugs (NSAIDs) on vascular endothelial growth factor (VEGF) gene expression in two osteoblast cell populations. DESIGN: Osteoblasts obtained by primary culture (HOp) and human osteosarcoma cell line MG63 (MG-63), which were treated with 10 µM doses of acetaminophen, indomethacin, ketoprofen, diclofenac, ibuprofen, ketorolac, naproxen or piroxicam. At 24 h of treatment, their gene expression of VEGF was evaluated by real-time polymerase chain reaction (RT-PCR) and compared with the expression in untreated cells (control group). RESULTS: The treatment with the different NSAIDs significantly reduced VEGF expression regardless of the cell line and NSAID studied. CONCLUSION: The results of this study suggest that these drugs may have undesirable effects on the osteoblast and its bone-forming capacity, given the effect of this growth factor on these cells. Further studies are warranted to determine their repercussions on bone tissue and to elucidate the cell signaling mechanism/s involved.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Osteoblasts/drug effects , Osteoblasts/metabolism , Vascular Endothelial Growth Factor A/metabolism , Adult , Cell Line , Cells, Cultured , Female , Gene Expression , Humans , Male , Real-Time Polymerase Chain Reaction
17.
PLoS One ; 13(4): e0196530, 2018.
Article in English | MEDLINE | ID: mdl-29698527

ABSTRACT

The reported incidence of osteoporosis is lower in countries in which the Mediterranean diet predominates, and this apparent relationship may be mediated by the phenolic compounds present in olive oil. The objective of this study was to determine the effect of phenolic extracts from different varieties of extra-virgin olive oil (Picual, Arbequina, Picudo, and Hojiblanca) on the differentiation, antigenic expression, and phagocytic capacity of osteoblast-like MG-63 cells. At 24 h of treatment a significant increase in phosphatase alkaline activity and significant reductions in CD54, CD80, and HLA-DR expression and in phagocytic activity were observed in comparison to untreated controls. The in vitro study performed has demonstrated that phenolic compounds from different extra virgin olive oil varieties can modulate different parameters related to osteoblast differentiation and function.


Subject(s)
Olea/chemistry , Osteoblasts/drug effects , Phenols/chemistry , Plant Extracts/pharmacology , Alkaline Phosphatase/metabolism , Cell Line , HLA-DR Antigens/metabolism , Humans , Intercellular Adhesion Molecule-1/metabolism , Olea/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism , Phagocytosis/drug effects
18.
Int J Med Sci ; 15(4): 359-367, 2018.
Article in English | MEDLINE | ID: mdl-29511371

ABSTRACT

The aim of the present study was to elucidate the role of osteoblasts in bisphosphonates-related osteonecrosis of the jaw (BRONJ). The specific objective was to evaluate the effect on osteoblasts of two nitrogen-containing BPs (zoledronate and alendronate) and one non-nitrogen-containing BP (clodronate) by analyzing modulations in their expression of genes essential for osteoblast physiology. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of zoledronate, alendronate, and clodronate at doses of 10-5, 10-7, or 10-9 M on the expression of Runx-2, OSX, ALP, OSC, OPG, RANKL, Col-I, BMP-2, BMP-7, TGF-ß1, VEGF, TGF-ßR1, TGF-ßR2, and TGF-ßR3 by primary human osteoblasts (HOBs) and MG-63 osteosarcoma cells. Expression of these markers was found to be dose-dependent, with no substantive differences between these cell lines. In general, results demonstrated a significant increase in TFG-ß1, TGF-ßR1, TGF-ßR2, TGF-ßR3, and VEGF expressions and a significant reduction in RUNX-2, Col-1, OSX, OSC, BMP-2, BMP-7, ALP, and RANKL expressions, while OPG expression varied according to the dose and cell line. The results of this in vitro study of HOBS and MG-63 cell lines indicate that low BP doses can significantly affect the expression of genes essential for osteoblast growth and differentiation and of genes involved in regulating osteoblast-osteoclast interaction, possibly by increasing TGF-ß1 production. These findings suggest that osteoblasts may play an important role in BRONJ development, without ruling out other factors.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Cell Differentiation/drug effects , Osteoblasts/drug effects , Osteoclasts/drug effects , Transforming Growth Factor beta1/genetics , Alendronate/pharmacology , Bisphosphonate-Associated Osteonecrosis of the Jaw/genetics , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology , Bone Morphogenetic Protein 2 , Bone Morphogenetic Protein 7 , Cell Proliferation/drug effects , Clodronic Acid/pharmacology , Diphosphonates/pharmacology , Gene Expression/drug effects , Humans , Imidazoles/pharmacology , Osteoblasts/metabolism , Osteoclasts/metabolism , Primary Cell Culture , Transforming Growth Factor beta1/biosynthesis , Zoledronic Acid
19.
Article in English | MEDLINE | ID: mdl-29437027

ABSTRACT

BACKGROUND AND OBJECTIVE: The preventive effects of olive oil against different diseases have been attributed to its high phenolic compound content. The objective of this study was to examine available scientific evidence on the beneficial effects against chronic diseases of olive oil phenolic compounds. METHOD: This article examines recently published data on olive oil phenolic compounds and their potential benefits in the prevention of cardiovascular disease, cancer, neurodegenerative disease, and osteoporosis. RESULTS: The antioxidant, anti-proliferative, pro-apoptotic, and anti-inflammatory activities of olive oil phenolic compounds have preventive effects against heart disease and cancer. These compounds also exert neuroprotective and neuromodulator effects against neurodegenerative disease, inhibiting the development of amyloid plaques. Finally, they are known to protect against osteoporosis, favoring bone regeneration. CONCLUSION: Dietary intake of olive oil can be recommended by healthcare professionals as an important source of phenolic compounds that play a role in the prevention of chronic disease and the consequent improvement in quality of life.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Bone Density Conservation Agents/administration & dosage , Cardiovascular Agents/administration & dosage , Cardiovascular Diseases/prevention & control , Diet, Healthy , Neoplasms/prevention & control , Neurodegenerative Diseases/prevention & control , Neuroprotective Agents/administration & dosage , Olive Oil/administration & dosage , Osteoporosis/prevention & control , Phenols/therapeutic use , Animals , Anti-Inflammatory Agents/administration & dosage , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/administration & dosage , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/isolation & purification , Cardiovascular Agents/adverse effects , Cardiovascular Agents/isolation & purification , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Humans , Neoplasms/metabolism , Neoplasms/pathology , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neuroprotective Agents/adverse effects , Neuroprotective Agents/isolation & purification , Olive Oil/adverse effects , Olive Oil/chemistry , Osteoporosis/metabolism , Osteoporosis/pathology , Phenols/adverse effects , Phenols/isolation & purification , Protective Factors , Risk Factors
20.
Eur J Clin Invest ; 48(4)2018 Apr.
Article in English | MEDLINE | ID: mdl-29392706

ABSTRACT

BACKGROUND: Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes individuals to an increased risk of fracture. Previous in vivo and in vitro studies have reported that phenolic compounds present in extra virgin olive oil have a beneficial effect on osteoblasts in terms of increase cell proliferation. The aim of this study was to determine whether phenolic compounds present in olive oil could modify the expression of cell differentiation markers on osteoblasts. STUDY DESIGN: An in vitro experimental design was performed using MG-63 osteoblasts cell line. METHODS: MG63 cells were exposed to different doses of luteolin, apigenin, or p-coumaric, caffeic or ferulic acid. Alkaline phosphatase (ALP) was evaluated by spectrophotometry and antigen expression (cluster of differentiation [CD] 54, CD80, CD86 and HLA-DR) by flow cytometry. RESULTS: At 24 hour, treated groups showed an increased ALP and modulated antigen profile, with respect to the nontreated group. CONCLUSION: These results demonstrate that the phenolic compounds studied induce cell maturation in vitro, increasing ALP synthesis and reducing the expression of antigens involved in immune functions of the osteoblast which would improve bone density.


Subject(s)
Coumaric Acids , Olive Oil/pharmacology , Osteoblasts/drug effects , Phenols/pharmacology , Alkaline Phosphatase/metabolism , Antigens, CD/metabolism , Apigenin/pharmacology , Caffeic Acids/pharmacology , Cell Differentiation/drug effects , Cell Line , Coumaric Acids/pharmacology , Dose-Response Relationship, Drug , Flow Cytometry , Humans , Luteolin/pharmacology , Osteoblasts/cytology , Propionates/pharmacology
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