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1.
Nutrients ; 13(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34684581

RESUMO

Osteoporosis has been discovered to be a risk factor for menopausal women. Although synbiotics (probiotics and prebiotics) are found in fermented soymilk-honey made using local probiotics, their effect on osteocalcin levels is still unknown. Therefore, this study's objective was to determine the influence of fermented soymilk-honey from different probiotics on osteocalcin levels. A 90-day pre-post quasi-experimental study with a control design was conducted on 54 postmenopausal women divided into three intervention groups namely, the soymilk (SM) group, the soymilk-honey fermented with Lactobacillus casei subsp. casei R-68 (SMH Lc) group, and the soymilk-honey fermented with Lactobacillus plantarum 1 R 1.3.2 (SMH Lp) group. Participants consumed 100 mL of soymilk (SM) or fermented soymilk with honey (SMH Lc or SMH Lp) for 90 days. At the beginning and end of the study, the blood serum osteocalcin level was measured and subjects' health status was assessed, such as cholesterol total, random blood glucose, and uric acid levels. Our results presented that in the SMH Lp group, 90 days supplementation of soy-honey milk fermented with Lactobacillus plantarum 1 R 1.3.2 significantly reduced the level of blood serum osteocalcin. Based on these results it is justified to perform more detailed studies on the effect of fermented soy-honey milk on bone health.


Assuntos
Fermentação , Mel , Menopausa/fisiologia , Osteocalcina/metabolismo , Probióticos/farmacologia , Leite de Soja/farmacologia , Idoso , Glicemia/metabolismo , Colesterol/sangue , Feminino , Humanos , Lactobacillus casei/fisiologia , Lactobacillus plantarum/fisiologia , Menopausa/sangue , Pessoa de Meia-Idade , Osteocalcina/sangue , Ácido Úrico/sangue
2.
PLoS One ; 16(10): e0258254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34610044

RESUMO

Epidemiology and pathogenesis of cardiovascular diseases (CVD) and osteoporosis are strikingly overlapping. This study presents matrix metalloproteinase-9 (MMP-9), as a simple molecular link more consistently associated with the pathophysiology of both osteoporosis and CVD risk factors. 40 adult female rats were randomly distributed into 4 groups [control sham-operated, untreated osteoporosis, carvedilol-treated osteoporosis and alendronate-treated osteoporosis]. After 8 weeks, blood samples were collected to estimate Lipid profile (Total cholesterol, HDL, Triglycerides), inflammatory markers (IL-6, TNF alpha, CRP and NO), and Bone turnover markers (BTM) (Alkaline phosphatase, osteocalcin and pyridinoline). The tibias were dissected to estimate MMP-9 and NF-kB gene expression, OPG, RANKL levels and for histological examination. Induction of osteoporosis resulted in a significant elevation in BTM, inflammatory markers and dyslipidemia. MMP-9 was significantly elevated and positively correlated with BTM, inflammation and dyslipidemia markers. Carvedilol and alendronate exerted a bone preservative role and attenuated dyslipidaemia and inflammation in accordance with their respective effect on MMP-9.


Assuntos
Doenças Cardiovasculares/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Osteoprotegerina/metabolismo , Ovariectomia , Ligante RANK/metabolismo , Fosfatase Alcalina/metabolismo , Aminoácidos/metabolismo , Animais , Remodelação Óssea/genética , Colesterol/sangue , Osso Cortical/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/sangue , Inflamação/patologia , Lipoproteínas HDL/sangue , Metaloproteinase 9 da Matriz/genética , NF-kappa B/metabolismo , Osteocalcina/metabolismo , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/genética , Ratos , Fatores de Risco , Tíbia/patologia , Triglicerídeos/sangue
3.
Nat Commun ; 12(1): 5296, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489478

RESUMO

The vascular endothelium is present within metabolic organs and actively regulates energy metabolism. Here we show osteocalcin, recognized as a bone-secreted metabolic hormone, is expressed in mouse primary endothelial cells isolated from heart, lung and liver. In human osteocalcin promoter-driven green fluorescent protein transgenic mice, green fluorescent protein signals are enriched in endothelial cells lining aorta, small vessels and capillaries and abundant in aorta, skeletal muscle and eye of adult mice. The depletion of lipoprotein receptor-related protein 1 induces osteocalcin through a Forkhead box O -dependent pathway in endothelial cells. Whereas depletion of osteocalcin abolishes the glucose-lowering effect of low-density lipoprotein receptor-related protein 1 depletion, osteocalcin treatment normalizes hyperglycemia in multiple mouse models. Mechanistically, osteocalcin receptor-G protein-coupled receptor family C group 6 member A and insulin-like-growth-factor-1 receptor are in the same complex with osteocalcin and required for osteocalcin-promoted insulin signaling pathway. Therefore, our results reveal an endocrine/paracrine role of endothelial cells in regulating insulin sensitivity, which may have therapeutic implications in treating diabetes and insulin resistance through manipulating vascular endothelium.


Assuntos
Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Glucose/metabolismo , Hiperglicemia/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Osteocalcina/genética , Animais , Células Endoteliais/patologia , Endotélio Vascular/patologia , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Teste de Tolerância a Glucose , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/deficiência , Masculino , Camundongos , Camundongos Knockout , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteocalcina/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais
4.
Int J Mol Sci ; 22(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34502245

RESUMO

Vitamin K and Vitamin K-dependent proteins (VKDPs) are best known for their pivotal role in blood coagulation. Of the 14 VKPDs identified in humans to date, 6 play also important roles in skeletal biology and disease. Thus, osteocalcin, also termed bone Gla-protein, is the most abundant non-collagenous protein in bone. Matrix Gla protein and Ucma/GRP on the other hand are highly abundant in cartilage. Furthermore, periostin, protein S, and growth arrest specific 6 protein (GAS 6) are expressed in skeletal tissues. The roles for these VKDPs are diverse but include the control of calcification and turnover of bone and cartilage. Vitamin K plays an important role in osteoporosis and serum osteocalcin levels are recognized as a promising marker for osteoporosis. On the other hand, matrix Gla protein and Ucma/GRP are associated with osteoarthritis. This review focuses on the roles of these three VKDPs, osteocalcin, matrix Gla protein and Ucma/GRP, in skeletal development and disease but will also summarize the roles the other skeletal VKDPs (periostin, protein S and GAS6) in skeletal biology.


Assuntos
Desenvolvimento Ósseo , Osteocalcina/metabolismo , Osteoporose/patologia , Vitamina K/metabolismo , Animais , Humanos , Osteoporose/metabolismo
5.
Chem Biol Interact ; 349: 109674, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34562440

RESUMO

We have assessed the molecular role of Rutin and rutin-Zn(II) complex on osteoblast differentiation and mineralization in human dental pulp cells and zebrafish model. The biocompatibility of the rutin-Zn(II) complex was determined using MTT and chick embryotoxicity assays. Alizarin red staining and ALP measurements were performed to study the osteogenic role of Rutin and rutin-Zn(II) complex at the cellular level in hDPSCs. At molecular level, following rutin and rutin-Zn(II) exposure, the mRNA expression profile of osteoblast markers such Runx2, type 1 col, OC, and ON were investigated. In addition to this, the expression of negative regulators of osteoblast development such Smad7, Smurf1, and HDAC7 waere studied by Real time RT-PCR analysis. The osteogenic role of prepared complex under in vivo was studied by an in-house zebrafish scale model followed by osteoblast differentiation markers expression profiling and Ca:P level measurement by ICP-MS. Rutin and the rutin-Zn(II) complex were found to be non-toxic till 10 µM and increased the expression of osteoblast differentiation marker genes. It also enhanced calcium deposition in both in vitro and in vivo models. Osteogenic property of rutin-Zn(II) in hDPSCs was found be mediated by Smad7, Smurf1, and HDAC7 and enhancing Runx2 expression. Our study warrants the possible use of rutin-Zn(II) as naïve agent or in combination with other bone scaffolding systems/materials for bone tissue engineering applications.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Osteogênese/efeitos dos fármacos , Rutina/química , Zinco/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Polpa Dentária/citologia , Humanos , Osteocalcina/genética , Osteocalcina/metabolismo , Proteína Smad7/genética , Proteína Smad7/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Peixe-Zebra/metabolismo
6.
Biomed Res Int ; 2021: 6684709, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195280

RESUMO

Adipose-derived mesenchymal stem cells (ADSCs) are a well-recognized multilineage stem cell with vital clinical feasibility for tissue regeneration. Extensive evidence indicates that oxidative stress and microRNAs (miRNAs/miRs) play an important role in the osteoinduction of adipose-derived mesenchymal stem cells. In this study, we investigated the mechanism of miR-125a-5p in regulating the osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) under oxidative stress. The expression of miR-125a-5p lessened gradually during the osteogenic differentiation of hADSCs. Relative to the negative group, the expression levels of runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osterix in the miR-125a-5p group were marked lower than those in the miR-125a-5p inhibitor group. The levels of p16, p21, p53, miR-125a-5p, and ROS during osteoinduction of hADSCs were assessed in vitro under oxidative stress and were observed to be upregulated. Further experiments showed that oxidative stress and miR-125a-5p together suppressed the expression of VEGF during osteogenic differentiation of hADSCs and that the inhibition of miR-125a-5p reversed the effect of oxidative stress. In short, our study indicated that miR-125a-5p is induced under oxidative stress and inhibits the expression of VEGF, leading to the reduction of osteogenic differentiation of hADSCs. Our outcomes showed that miR-125a-5p could be a potential clinical target for bone repairing.


Assuntos
Adipócitos/citologia , Células-Tronco Mesenquimais/citologia , MicroRNAs/metabolismo , Estresse Oxidativo , Fosfatase Alcalina/metabolismo , Remodelação Óssea , Osso e Ossos/metabolismo , Diferenciação Celular , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteogênese/fisiologia , Fator de Transcrição Sp7/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
7.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34062952

RESUMO

BACKGROUND: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier "polybutylcyanoacrylate" (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. METHODOLOGY: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. RESULTS: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of -1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. CONCLUSION: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.


Assuntos
Embucrilato/química , Mandíbula/crescimento & desenvolvimento , Nanopartículas/química , Osteogênese , Tiofenos/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Mandíbula/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas/ultraestrutura , Imagem Óptica , Osteocalcina/metabolismo , Tamanho da Partícula , Ratos Sprague-Dawley , Eletricidade Estática
8.
Theranostics ; 11(14): 6717-6734, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093849

RESUMO

Rationale: Osteoporotic patients suffer symptoms of excessive osteoclastogenesis and impaired osteogenesis, resulting in a great challenge to treat osteoporosis-related bone defects. Based on the positive effect of rare earth elements on bone metabolism and bone regeneration, we try to prove the hypothesis that the La3+ dopants in lanthanum-substituted MgAl layered double hydroxide (La-LDH) nanohybrid scaffolds simultaneously activate osteogenesis and inhibit osteoclastogenesis. Methods: A freeze-drying technology was employed to construct La-LDH nanohybrid scaffolds. The in vitro osteogenic and anti-osteoclastogenic activities of La-LDH nanohybrid scaffolds were evaluated by using ovariectomized rat bone marrow stromal cells (rBMSCs-OVX) and bone marrow-derived macrophages (BMMs) as cell models. The in vivo bone regeneration ability of the scaffolds was investigated by using critical-size calvarial bone defect model of OVX rats. Results: La-LDH nanohybrid scaffolds exhibited three-dimensional macroporous structure, and La-LDH nanoplates arranged perpendicularly on chitosan organic matrix. The La3+ dopants in the scaffolds promote proliferation and osteogenic differentiation of rBMSCs-OVX by activating Wnt/ß-catenin pathway, leading to high expression of ALP, Runx-2, COL-1 and OCN genes. Moreover, La-LDH scaffolds significantly suppressed RANKL-induced osteoclastogenesis by inhibiting NF-κB signaling pathway. As compared with the scaffolds without La3+ dopants, La-LDH scaffolds provided more favourable microenvironment to induce new bone in-growth along macroporous channels. Conclusion: La-LDH nanohybrid scaffolds possessed the bi-directional regulation functions on osteogenesis and osteoclastogenesis for osteoporotic bone regeneration. The modification of La3+ dopants in bone scaffolds provides a novel strategy for osteoporosis-related bone defect healing.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Lantânio/farmacologia , Nanoestruturas/química , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Tecidos Suporte/química , Animais , Regeneração Óssea/genética , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Dioxigenases/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Lantânio/química , Macrófagos/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Transmissão , NF-kappa B/metabolismo , Nanoestruturas/ultraestrutura , Osteocalcina/metabolismo , Osteogênese/genética , Osteoporose/metabolismo , Ligante RANK/farmacologia , Ratos , Ratos Sprague-Dawley , Tomografia Computadorizada por Raios X , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
9.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067898

RESUMO

The aim of the study was to examine the efficacy of cold atmospheric plasma (CAP) on the mineralization and cell proliferation of murine dental cementoblasts. Cells were treated with CAP and enamel matrix derivates (EMD). Gene expression of alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (BGLAP), periostin (POSTN), osteopontin (OPN), osterix (OSX), collagen type I alpha 1 chain (COL1A1), dentin matrix acidic phosphoprotein (DMP)1, RUNX family transcription factor (RUNX)2, and marker of proliferation Ki-67 (KI67) was quantified by real-time PCR. Protein expression was analyzed by immunocytochemistry and ELISA. ALP activity was determined by ALP assay. Von Kossa and alizarin red staining were used to display mineralization. Cell viability was analyzed by XTT assay, and morphological characterization was performed by DAPI/phalloidin staining. Cell migration was quantified with an established scratch assay. CAP and EMD upregulated both mRNA and protein synthesis of ALP, POSTN, and OPN. Additionally, DMP1 and COL1A1 were upregulated at both gene and protein levels. In addition to upregulated RUNX2 mRNA levels, treated cells mineralized more intensively. Moreover, CAP treatment resulted in an upregulation of KI67, higher cell viability, and improved cell migration. Our study shows that CAP appears to have stimulatory effects on regeneration-associated cell functions in cementoblasts.


Assuntos
Cementogênese/efeitos dos fármacos , Cemento Dentário/metabolismo , Gases em Plasma/farmacologia , Animais , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Camundongos , Osteocalcina/metabolismo , Osteopontina/metabolismo , Gases em Plasma/metabolismo , Transcriptoma/genética
10.
Ann Agric Environ Med ; 28(2): 326-330, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34184518

RESUMO

INTRODUCTION: Estrogen deficiency found in postmenopausal women may lead to disturbances in the balance of bone metabolism. Study of the influence of estradiol on markers of bone turnover may help to understand the mechanisms of bone metabolism and to monitor osteoporosis therapy in postmenopausal women at high risk of fractures. The aim of the study was evaluation of the effect of estradiol on the basic markers of bone turnover in postmenopausal women. MATERIAL AND METHODS: The study was conducted in a group of 92 postmenopausal women, divided into two groups: Gr-1 with low estradiol levels ≤ 10 pg/ml and Gr-2 with reference estradiol levels ≥ 25 pg/ml). Basic markers of bone turnover were examined: Ctx (C-terminal cross-linked telopeptide of type I collagen alpha chain) and OC (osteocalcin); pro-resorptive cytokines: IL-6 and TNF-α; vitamin 25(OH)D3 and lipid profile. Women was also analyzed according to demographic and clinical data. RESULTS: A positive relationship was found between estradiol and the main bone formation marker - OC (p = 0.041, r = 0.213) and IL-6, TNF-α (p = 0.007, r = 0.281 and p = 0.018, r = 0.246, respectivly, but only in the group with a reference hormone level. Moreover, the main markers of bone turnover: Ctx and OC showed a mutual positive correlation (p = 0.013; r = 0.257) in women with reference estradiol levels. Relationships between markers of bone remodeling, pro-resorptive cytokines and vitamin D3 depending on the level of estradiol showed no statistically significant correlation. CONCLUSIONS: The study showed that only in women with the reference estradiol level (≥ 25 pg/ml) were the bone formation and resorption processes balanced.


Assuntos
Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Feminino , Humanos , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Osteocalcina/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/fisiopatologia , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo , Vitamina D/metabolismo
11.
Nutrients ; 13(5)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068953

RESUMO

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation. We hypothesized that a high fat diet (60%) administered to developing male C57BL/6J mice that had not reached skeletal maturity would over represent bone microarchitectural implications, and that skeletally mature mice would better represent adult-onset glucose intolerance and the pre-diabetes phenotype. Two groups of developing (8 week) and mature (12 week) male C57BL/6J mice were placed onto either a normal chow (NC) or high fat diet (HFD) for 10 weeks. Oral glucose tolerance tests were performed throughout the study period. Long bones were excised and analysed for ex vivo biomechanical testing, micro-computed tomography, 2D histomorphometry and gene/protein expression analyses. The HFD increased fasting blood glucose and significantly reduced glucose tolerance in both age groups by week 7 of the diets. The HFD reduced biomechanical strength, both cortical and trabecular indices in the developing mice, but only affected cortical outcomes in the mature mice. Similar results were reflected in the 2D histomorphometry. Tibial gene expression revealed decreased bone formation in the HFD mice of both age groups, i.e., decreased osteocalcin expression and increased sclerostin RNA expression. In the mature mice only, while the HFD led to a non-significant reduction in runt-related transcription factor 2 (Runx2) RNA expression, this decrease became significant at the protein level in the femora. Our mature HFD mouse model more accurately represents late-onset impaired glucose tolerance/pre-T2DM cases in humans and can be used to uncover potential insights into reduced bone formation as a mechanism of skeletal fragility in these patients.


Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Dieta Hiperlipídica/efeitos adversos , Animais , Glicemia , Peso Corporal , Subunidade alfa 1 de Fator de Ligação ao Core , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Intolerância à Glucose , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteocalcina/metabolismo , Microtomografia por Raio-X
12.
J Orthop Surg Res ; 16(1): 359, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078411

RESUMO

BACKGROUND: WNT1 c.110 T>C and c.505G>T missense mutations have been identified in patients with osteogenesis imperfecta (OI). Whether these mutations affect osteoblast differentiation remains to be determined. This study aimed to investigate the effects of WNT1 c.110 T>C and c.505G>T mutations on osteoblast function, gene expression, and pathways involved in OI. METHODS: Empty vector (negative control), wild-type WNT1, WNT1 c.110 T>C, WNT1 c.505G>T, and WNT1 c.884C>A (positive control) mutant plasmids were constructed and transfected into preosteoblast (MC3T3-E1) cells to investigate their effect on osteoblast differentiation. The expressions of osteoblast markers, including BMP2, RANKL, osteocalcin, and alkaline phosphatase (ALP), were determined using quantitative real-time polymerase chain reaction (RT-qPCR), western blotting (WB), enzyme-linked immunosorbent assay, and ALP staining assay, respectively. The mRNA and protein expression levels of WNT1 or the expression levels of the relevant proteins involved in the WNT1/ß-catenin signaling pathway were also determined using RT-qPCR, WB, and immunofluorescence (IF) assays after the different plasmids were transfected into MC3T3-E1 cells. RESULTS: Compared with those in the wild-type group, in the mutation groups, the mRNA and protein expression levels of BMP2 were suppressed, the expressions of osteocalcin and ALP were inhibited, and the mRNA and protein expression levels of RANKL were enhanced in MC3T3-E1 cells. WB and IF assays revealed that the protein expression levels of WNT1 in MC3T3-E1 cells were downregulated in the mutation groups compared with those in the wild-type WNT1 group. Furthermore, the expression levels of nonphosphorylated ß-catenin (non-p-ß-catenin) and phosphorylated GSK-3ß (p-GSK-3ß) were downregulated in the mutation groups compared with those in the wild-type group. However, no significant changes in the expression level of non-p-ß-catenin or p-GSK-3ß were observed in the mutation groups. CONCLUSIONS: WNT1 c.110 T>C and c.505G>T mutations may alter the proliferation and osteogenic phenotype of MC3T3-E1 linked to the progression of OI via the inhibition of the WNT1/ß-catenin signaling pathway. This is the first study to confirm the effect of WNT1 c.110 T>C and c.505G>T missense mutations on osteoblast differentiation and propose a new molecular mechanism for OI development.


Assuntos
Diferenciação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Expressão Gênica/genética , Mutação de Sentido Incorreto/genética , Osteoblastos/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteína Wnt1/genética , Proteína Wnt1/metabolismo , beta Catenina/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Células Cultivadas , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Osteocalcina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo
13.
J Orthop Surg Res ; 16(1): 362, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098995

RESUMO

BACKGROUND: Bone fractures are medical emergencies that require prompt intervention to help return bone to its normal function. Various methods and treatments have been utilized to increase the speed and efficiency of bone repair. This study aimed to investigate the treatment effects of Prunus dulcis aqueous extract on tibial bone healing in rabbits. METHODS: All animals were distributed in five groups with six rats in each group, including the sham group, the control group in which tibial lesion was made and received distilled water, treatment groups with 150 mg kg-1, 300 mg kg-1 doses of Prunus dulcis extract, and osteocare treated group. Biochemical blood factors including calcium, phosphorus, and alkaline phosphatase (on days 0, 10, 30, and 50), biomarkers of oxidative stress such as GPx, CAT, and MDA (on days 10 and 30), radiological evaluation, histopathological parameters, and osteocalcin immunohistochemical expression were assessed. RESULTS: The data showed calcium levels in the treatment groups increased significantly from day 10 to day 50, respectively, and blood phosphorus levels decreased from day 10 to day 50 in the treatment groups. Alkaline phosphatase initially increased and then decreased in treatment groups. In the treatment groups, GPx and CAT levels significantly increased, and the serum amount of MDA reduced. The best antioxidant results were related to the extract-treated group with a higher dose. Radiographic score was significantly higher in the treatment groups than the control group on day 30. Based on the pathological findings, the healing occurred faster in the extract-treated group with a higher dose. Osteocalcin expression was significantly higher in the control group than that in the treatment groups. CONCLUSIONS: Treatment with Prunus dulcis extract with a dosage of 300 mg/kg accelerated tibial bone healing in rabbits.


Assuntos
Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Prunus dulcis/química , Tíbia/fisiopatologia , Fraturas da Tíbia/tratamento farmacológico , Fraturas da Tíbia/fisiopatologia , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes , Regeneração Óssea/efeitos dos fármacos , Masculino , Osteocalcina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Tíbia/fisiologia , Fraturas da Tíbia/metabolismo , Água
14.
Medicine (Baltimore) ; 100(21): e26153, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032772

RESUMO

ABSTRACT: Although the incidence is lower in men than women, osteoporosis remains a significant health issue in men as it may give rise to severe complications if not managed appropriately. As men and women show different biological and social backgrounds, we retrospectively evaluated the differences in the bone metabolism between men and women using bone biomarkers.Bone mineral density (BMD) was determined in all patients using dual-energy X-ray absorptiometry (DXA) and analyzing various bone biomarkers such as carboxyl-terminal collagen crosslinks (CTX), osteocalcin (OCT), and alkaline phosphatase (ALP). The CTX/OCT ratio was used to estimate the association between bone absorption and formation.OCT, CTX, and ALP levels were elevated in patients with osteoporosis. Women displayed a higher incidence of osteoporosis and greater reduction in BMD than men. The mean OCT level in men was lower than that in women. Moreover, men showed significantly lower OCT levels than women of aged 65 and under 80 years old. Among patients with osteoporosis, men had a higher ratio of bone markers than women.Levels of biomarkers of bone formation and absorption were increased in the osteoporosis group. However, men showed lower increases in bone formation biomarkers than did women, indicating that the rate of bone formation relative to bone absorption did not increase in men compared with that in women. Therefore, we suggest that men and women have different bone metabolism in old age.


Assuntos
Osso e Ossos/metabolismo , Osteoporose/metabolismo , Caracteres Sexuais , Absorciometria de Fóton , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Densidade Óssea , Reabsorção Óssea , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Masculino , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteoclastos/metabolismo , Osteogênese , Osteoporose/diagnóstico por imagem , Fragmentos de Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Estudos Retrospectivos
15.
Methods Mol Biol ; 2325: 97-106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34053053

RESUMO

Immune and bone cells cross talk has been established by different years; however the underlying mechanisms require continuous investigation. To this end both in vivo and in vitro models have been realized and some of this are described in this chapter. In particular, here we described the animal models used for the understanding of lymphocyte role in bone homeostasis, together with some in vitro models.


Assuntos
Linfócitos B/imunologia , Remodelação Óssea , Osteoclastos/metabolismo , Osteócitos/metabolismo , Osteogênese , Linfócitos T/imunologia , Fosfatase Alcalina/metabolismo , Animais , Linhagem Celular , Colágeno Tipo I/metabolismo , Homeostase , Humanos , Camundongos , Osteocalcina/metabolismo , Fosfatase Ácida Resistente a Tartarato/metabolismo , Tomografia Computadorizada por Raios X/métodos
16.
Clin Nephrol ; 96(2): 96-104, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34042581

RESUMO

AIM: Bone mineral disorders are being increasingly seen among diabetic populations as the frequency of diabetes mellitus (DM) is rising at an alarming rate. Our aim is to examine the relationship between glycemic control and bone turnover markers like osteocalcin (OC), C-terminal carboxy telopeptide (CTX), and bone-specific alkaline phosphatase (ALP) in patients with type 2 diabetes, and the effects of anti-diabetic regimens on these markers. MATERIALS AND METHODS: A total of 80 newly diagnosed type 2 DM patients were enrolled into the study and divided into two groups according to glucose regulation (group 1 HbA1c < 7 and group 2 HbA1c ≥ 7). They were also classified into three groups according to antidiabetic regimen. Physical examination findings, demographic characteristics, and anti-diabetic regimens of the patients were recorded. Hemogram and biochemical parameters were studied after 12 hours of fasting. Serum levels OC and CTX were examined by ELISA method. Bone-specific ALP was examined by Chemiluminesence immuneassay (CLIA) method. Bone densitometry was performed on the 2016 model Stratos DR device of DMS brand, and T scores of the patients were recorded. All parameters were repeated at the 6th month of the study. RESULTS: Serum vitamin D and OC levels of group 1 were higher, while ALP was higher in group 2. However, we failed to determine a significant difference in CTX levels between the groups. OC levels were enhanced only in patients receiving metformin plus vildagliptin therapy. The CTX levels increased in all groups, whereas they decreased in the metformin plus DPP-4 group. CONCLUSION: Better glucose regulation is associated with better bone formation, and among three groups metformin plus vildagliptin therapy has a favorable effect on both bone formation and resorption.


Assuntos
Glicemia/metabolismo , Remodelação Óssea/fisiologia , Colágeno Tipo I/metabolismo , Diabetes Mellitus Tipo 2 , Hipoglicemiantes/uso terapêutico , Peptídeos/metabolismo , Fosfatase Alcalina/metabolismo , Biomarcadores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Controle Glicêmico , Humanos , Osteocalcina/metabolismo
17.
J Clin Endocrinol Metab ; 106(9): e3506-e3518, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34003927

RESUMO

CONTEXT: The osteoblast-derived polypeptide, osteocalcin (OC), has been associated with lower risk of type 2 diabetes and metabolic syndrome (MetS) in several epidemiological studies. Animal studies have indicated the undercarboxylated form of OC (ucOC) drives its association with metabolic outcomes. OBJECTIVE: We compared associations of ucOC and carboxylated OC (cOC) with MetS and its components in older men. METHODS: A cross-sectional analysis of 2575 men aged ≥70 years and older resident in Perth, Western Australia. ucOC was assayed using a hydroxyapatite-binding method, and cOC calculated by subtracting ucOC from total OC. Main outcome measures were MetS and its components. RESULTS: Both lower serum ucOC and cOC levels, and the proportion of cOC (%cOC) were associated with less favorable metabolic parameters (higher waist circumference, triglyceride, glucose, blood pressure, and lower high-density lipoprotein cholesterol), whereas inverse associations were found with %ucOC. Men in the lowest quintile of ucOC had higher risk of MetS compared to men in the highest quintile (Q1 ≤ 7.7 vs Q5 > 13.8 ng/mL; OR = 2.4; 95% CI, 1.8-3.2). Men in the lowest quintile of cOC had higher risk of MetS compared to those in the highest quintile (≤ 5.8 vs > 13.0 ng/mL; OR = 2.4; 95% CI, 1.8-3.2). CONCLUSION: Lower concentrations of serum ucOC or cOC were associated with less favorable metabolic parameters and a higher risk of MetS. In contrast, a lower proportion of ucOC was associated with better metabolic parameters and lower MetS risk. Further research is warranted to determine whether ucOC and cOC are suitable biomarkers for cardiometabolic risk in men.


Assuntos
Síndrome Metabólica/metabolismo , Osteocalcina/metabolismo , Idoso , Biomarcadores , Glicemia/análise , Pressão Sanguínea , HDL-Colesterol/sangue , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Circunferência da Cintura , Austrália Ocidental
18.
Sci Rep ; 11(1): 8418, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875709

RESUMO

We have previously shown that parathyroid hormone (PTH) induces the phosphorylation of the DNA-binding protein Nascent polypeptide associated complex And Coregulator alpha (NACA), leading to nuclear translocation of NACA and activation of target genes. Using ChIP-Seq against NACA in parallel with RNA-sequencing, we report the identification of Ubiquitin Specific Peptidase 53 (Usp53) as a target gene of PTH-activated NACA in osteoblasts. A binding site for NACA within the ChIP fragment from the Usp53 promoter was confirmed by electrophoretic mobility shift assay. Activity of the Usp53 promoter (- 2325/+ 238 bp) was regulated by the JUN-CREB complex and this activation relied on activated PKA and the presence of NACA. Usp53 knockdown in ST2 stromal cells stimulated expression of the osteoblastic markers Bglap2 (Osteocalcin) and Alpl (Alkaline phosphatase) and inhibited expression of the adipogenic markers Pparg and Cebpa. A similar effect was measured when knocking down Naca. During osteoblastogenesis, the impact of Usp53 knockdown on PTH responses varied depending on the maturation stage of the cells. In vivo implantation of Usp53-knockdown bone marrow stromal cells in immunocompromised mice showed an increase in osteoblast number and a decrease in adipocyte counts. Our data suggest that Usp53 modulates the fate of mesenchymal cells by impacting lineage selection.


Assuntos
Adipócitos/metabolismo , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Adipogenia , Fosfatase Alcalina/metabolismo , Animais , Camundongos , Osteocalcina/metabolismo , Hormônio Paratireóideo/metabolismo
19.
Biomed Res Int ; 2021: 3582342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834063

RESUMO

In the field of biology and medicine, one hears often about stem cells and their potential. The dental implant new surfaces, subjected to specific treatments, perform better and allow for quicker healing times and better clinical performance. The purpose of this study is to evaluate from a biological point of view the interaction and cytotoxicity between stem cells derived from dental pulp (DPSCs) and titanium surfaces. Through the creation of complex cells/implant, this study is aimed at analyzing the cytotoxicity of dental implant surfaces (Myth (Maipek Manufacturer Industrial Care, Naples, Italy)) and the adhesion capacity of cells on them and at considering the essential factors for implant healing such as osteoinduction and vasculogenesis. These parameters are pointed out through histology (3D cell culture), immunofluorescence, proliferation assays, scanning electron microscopy, and PCR investigations. The results of the dental implant surface and its interaction with the DPSCs are encouraging, obtaining results increasing the mineralization of the tissues. The knowledge of this type of interaction, highlighting its chemical and biological features, is certainly also an excellent starting point for the development of even more performing surfaces for having better healing in the oral surgical procedures related to dental implant positioning.


Assuntos
Implantes Dentários , Polpa Dentária/citologia , Células-Tronco/citologia , Matriz Óssea/efeitos dos fármacos , Matriz Óssea/metabolismo , Adesão Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Osteocalcina/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/ultraestrutura , Propriedades de Superfície , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Lupus ; 30(7): 1116-1123, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33832361

RESUMO

OBJECTIVE: To investigate the mechanism underlying systemic lupus erythematosus (SLE)-related bone loss by evaluating the bone mineral density (BMD) and bone turnover markers (BTMs) in premenopausal patients with new-onset SLE without any treatment. METHODS: BMD and BTMs of 106 premenopausal patients with new-onset SLE and 64 gender-, age- and body mass index (BMI)-matched healthy controls were analyzed. BMD was determined using dual energy X-ray absorptiometry (DXA). Serum BTMs were measured. RESULTS: Hip and lumbar spine BMD in premenopausal patients with new-onset SLE was significantly decreased compared with healthy controls. Higher rate of osteoporosis was observed in new-onset SLE patients (25% vs. 1%). Moreover, uncoupled bone remodeling evidenced by an increase in bone resorption marker ß-CTX (685.9 ± 709.6 pg/mL vs. 395.4 ± 326.0 pg/mL, P < 0.05) and decrease in bone formation markers PINP (37.4 ± 33.0 ng/mL vs. 46.1 ± 20.9 ng/mL, P < 0.05) and OC (11.4 ± 9.8 ng/mL vs. 18.2 ± 8.6 ng/mL, P < 0.05) was observed in premenopausal patients with new-onset SLE compared with healthy controls. Univariate correlation analyses showed negative correlations between OC and SLE Disease Activity Index (SLEDAI), and positive correlations between ß-CTX and SLEDAI. SLE patients positive for dsDNA, nucleosome showed lower OC and higher ß-CTX. CONCLUSION: Premenopausal patients with new-onset SLE had decreased BMD and abnormal bone metabolism with increased ß-CTX and decreased OC and P1NP levels, indicating uncoupled bone remodeling in new-onset SLE patients. Disease activity and abnormal immunity, especially the amount of antibodies in SLE patients, were strongly associated with abnormality of bone metabolism.


Assuntos
Biomarcadores/sangue , Remodelação Óssea/fisiologia , Osso e Ossos/metabolismo , Lúpus Eritematoso Sistêmico/complicações , Osteoporose Pós-Menopausa/etiologia , Absorciometria de Fóton/métodos , Adulto , Índice de Massa Corporal , Densidade Óssea/fisiologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Estudos de Casos e Controles , China/epidemiologia , Colágeno/metabolismo , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Osteocalcina/metabolismo , Osteoporose/complicações , Osteoporose Pós-Menopausa/diagnóstico , Ossos Pélvicos/diagnóstico por imagem , Fragmentos de Peptídeos/metabolismo , Pré-Menopausa , Pró-Colágeno/metabolismo , Índice de Gravidade de Doença
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