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1.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(5): 501-509, 2021 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34636196

RESUMO

The maintenance of bone homeostasis is critical for bone health. It is vulnerable to cause bone loss, even severely osteoporosis when the balance between bone formation and absorption is interrupted. Growing evidence has shown that energy metabolism disorders, such as abnormal glucose metabolism, irregular amino acid metabolism, and aberrant lipid metabolism, can damage bone homeostasis, causing or exacerbating bone mass loss and osteoporosis-related fractures. Here, we summarize the studies of energy metabolism in osteoblasts and osteoclasts and provide a better appreciation of how energy metabolism, especially glucose metabolism maintains bone homeostasis. With this knowledge, new avenues will be unraveled to understand and cue bone-related diseases such as osteoporosis.


Assuntos
Osteoblastos , Osteoclastos , Osso e Ossos , Metabolismo Energético , Osteogênese
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 55(9): 1123-1128, 2021 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-34619931

RESUMO

Objective: To investigate the role of autophagy mediated by mTOR signaling pathway in the inhibition of osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by cadmium. Methods: HBMSCs were divided into 0, 2.5 or 5.0 µmol/L groups according to the exposure dose of cadmium chloride (CdCl2), and each group was treated for 1 day, 4 days and (or) 7 days. The ALP activity and mRNA and protein expression levels of osteogenesis markers (ALP, RUNX2 and OSTERIX), autophagy-related proteins (LC3 and Beclin-1) and mTOR signaling pathway related proteins (mTOR, p-mTOR and p-p70S6K) expression, alkaline phosphatase staining and alizarin red staining were detected. MHY 1485 was selected as the signaling pathway activator. The control group, CdCl2 group (5.0 µmol/L), MHY 1485 group and CdCl2+MHY 1485 combined treatment group were set. After 7 days of treatment, the expression levels of autophagy related proteins and mTOR signaling pathway related proteins of hBMSCs in each group were detected. Results: There was no significant difference in ALP activity between 0, 2.5 and 5.0 µmol/L groups on day 1 and 4 (P>0.05); On day 7, compared with the 0 µmol/L group, the ALP activity, expression of osteogenic markers (ALP, RUNX2, OSTERIX) and mTOR signaling pathway related proteins (mTOR, p-mTOR, p-p70S6K) expression decreased in the 2.5 and 5.0 µmol/L group (P<0.05). Compared with the 0 µmol/L group, the staining of the 2.5 and 5.0 µmol/L groups became lighter, and the formation of ALP and mineralized nodules was reduced. Compared with the CdCl2 group, the autophagy related protein expression in the CdCl2+MHY 1485 combined treatment group decreased, and the mTOR signaling pathway related protein expression increased. The difference was statistically significant (P<0.05). Conclusion: The inhibition of osteogenic differentiation of hBMSCs by cadmium may be related to autophagy mediated by mTOR signaling pathway.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Autofagia , Cádmio , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
3.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(9): 1394-1399, 2021 Aug 31.
Artigo em Chinês | MEDLINE | ID: mdl-34658355

RESUMO

OBJECTIVE: To investigate the association of the expressions of RUNX2/LAPTM5 with osteogenesis and lysosomes in osteoblastic cells during mineralization induction. METHODS: MC3T3- E1 cells cultured in osteogenic induction medium was examined for mineralization and osteogenic differentiation using Alizarin red staining and alkaline phosphatase (ALP) staining, respectively. RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of Runx2 and LAPTM5 in the cells during osteogenic induction for 5 days. The effects of overexpression and interference of RUNX2/ LAPTM5 on the expressions of ALP and osteocalcin (OCN) in the cells were examined with Western blotting. RESULTS: MC3T3- E1 cells cultured in osteogenic induction medium showed an increased number of mineralized nodules over time, and the size of the mineralized nodules increased as the culture time extended; the number of purple-blue granules stained by ALP also increased gradually with time. RT-qPCR and Western blotting showed that the expressions of RUNX2 and LAPTM5 in the cells increased progressively during osteogenic mineralization (P < 0.001). Overexpression and interference of RUNX2 obviously affected LAPTM5 expression in the cells (P < 0.05); modulation of LAPTM5 expression did not significantly affect RUNX2 expression but caused significant changes in ALP and OCN expressions (P < 0.01). CONCLUSION: RUNX2 /LAPTM5 may participate in the regulation of osteoblast differentiation, and RUNX2 may be involved in the regulation of LAPTM5 expression. RUNX2 /LAPTM5 may play a mediating role in the process of osteogenic mineralization involving lysosomes.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , Osteogênese , Diferenciação Celular , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteoblastos , Osteocalcina/genética
4.
Mater Sci Eng C Mater Biol Appl ; 128: 112255, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474817

RESUMO

OBJECTIVES: The aim of this work was to combine engineered hard and soft tissue, adopting a new method for interfacial adhesion of osteo-mucosal construct. We hypothesized that the chemical procedure involved in this method not only adheres the components, but also improves the cell growth inside them. METHODS: 3D-printed functionally-graded porous hard-tissue scaffolds were characterized, functionalized by aminolysis and tyrosinase, and accommodated by human osteoblast cells. Introducing amino groups through aminolysis and inducing dopaquinones by tyrosinase can take part in the Michael additions to cause the adhesion. Subsequently, fully-differentiated engineered oral mucosa was formed directly on the surface of hard tissue. Constructs were assessed in term of morphology, structure, chemical composition, histology, and cytocompatibility. Interfacial adhesion was compared to a control group prepared by using a biological glue for the attachment of the soft and hard tissues. RESULTS: The data confirmed higher proliferation of osteoblast cells via aminolysis and improved osteoblast cells distribution and differentiation by incorporation of tyrosinase in collagen. There was evidence of multilayered, stratified epithelium on the osteo-mucosal model with viable fibroblasts and osteoblasts within the lamina propria and bone tissue layers. Our method of adhesion resulted in cohesive debonding within the engineered soft tissue; while in the control group, adhesive debonding and complete separation of the oral mucosa from the hard tissue was observed. Although the shear strength of the osteo-mucosal model (157.6 kDa ± 25.1) was slightly higher than that of the control group (149.4 kDa ± 23.1), there was no statistically significant difference between them (p > 0.05). However, the advantage of our in situ adhesion approach is the absence of a barrier like glue which can disrupt direct cellular communications between tissues. SIGNIFICANCE: This study provides a novel method of directly combining tissue-engineered human bone with oral mucosa, which has the potential to improve cell-ingrowth and tissue integration. This engineered tissue construct, after further optimization, can be used clinically as a graft material in various oral surgeries and can also be employed as an in vitro model to investigate many aspects of oral diseases and examine dental materials and oral health care products as a replacement of in vivo models.


Assuntos
Engenharia Tecidual , Tecidos Suporte , Humanos , Mucosa Bucal , Osteoblastos , Porosidade
5.
Mater Sci Eng C Mater Biol Appl ; 128: 112289, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474840

RESUMO

Successful osseointegration, i.e. the fully functional connection of patient's bone and artificial implant depends on the response of the cells to the direct contact with the surface of the implant. The surface properties of the implant which trigger cell responses leading to its integration into the surrounding bone can be tailored by surface modifications or coating with thin layers. One potential material for such applications is ultrananocrystalline diamond (UNCD). It combines the exceptional mechanical properties of diamond with good biocompatibility and possibility of coating as thin uniform films on different substrates of biological interest. In the current work we firstly deposited UNCD films on titanium-coated substrates and applied oxygen or ammonia plasma to modify their surface properties. The as-grown and modified UNCD exhibited relatively smooth surfaces with topography dominated by rounded features. The modifications induced oxygen- or amino-terminated surfaces with increased hydrophilicity. In addition, the UNCD coatings exhibited very low coefficient of friction when diamond was used as a counterpart. As-grown and modified UNCD samples were applied to study the responses of human osteoblast MG63 cells triggered by surfaces with various terminations assessed by proteomic analysis. The results revealed that the coating of Ti with UNCD as well as the plasma modifications resulting in O- or NH2-terminated UNCD induced upregulation of proteins specific for cytoskeleton, cell membrane, and extracellular matrix (ECM) involved in the cell-ECM-surface interactions. Proteins from each of these groups, namely, vimentin, cadherin and fibronectin were further studied immunocytochemically and the results confirmed their increased abundance leading to improved cell-to-surface adhesion and cell-to-cell interactions. These findings demonstrate the potential of implant coating with UNCD and its surface modifications for better osseointegration and bone formation.


Assuntos
Proteoma , Titânio , Diamante , Humanos , Osteoblastos , Proteômica , Propriedades de Superfície
6.
Mater Sci Eng C Mater Biol Appl ; 128: 112309, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474860

RESUMO

Recently, black phosphorus (BP) has garnered great attention as one of newly emerging two-dimensional nanomaterials. Especially, the degraded platelets of BP in the physiological environment were shown to be nontoxic phosphate anions, which are a component of bone tissue and can be used for mineralization. Here, our study presents the potential of BP as biofunctional and biocompatible nanomaterials for the application to bone tissue engineering and regeneration. An ultrathin layer of BP nanodots (BPNDs) was created on a glass substrate by using a flow-enabled self-assembly process, which yielded a highly uniform deposition of BPNDs in a unique confined geometry. The BPND-coated substrates represented unprecedented favorable topographical microenvironments and supportive matrices suitable for the growth and survival of MC3T3-E1 preosteoblasts. The prepared substrates promoted the spontaneous osteodifferentiation of preosteoblasts, which had been confirmed by determining alkaline phosphatase activity and extracellular calcium deposition as early- and late-stage markers of osteogenic differentiation, respectively. Furthermore, the BPND-coated substrates upregulated the expression of some specific genes (i.e., RUNX2, OCN, OPN, and Vinculin) and proteins, which are closely related to osteogenesis. Conclusively, our BPND-coating strategy suggests that a biologically inert surface can be readily activated as a cell-favorable nanoplatform enabled with excellent biocompatibility and osteogenic ability.


Assuntos
Osteoblastos , Osteogênese , Diferenciação Celular , Fósforo , Engenharia Tecidual
7.
Mater Sci Eng C Mater Biol Appl ; 128: 112315, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474866

RESUMO

Implant surface plays a crucial role in improving osseointegration and long-term implant life. When the implant comes in contact with the bone tissue, the bone marrow mesenchymal cells interact with the implant surface and the surface properties such as morphology, wettability, mechanical properties and chemistry influences cell migration, proliferation and differentiation. Different surface modification strategies such as ceramic coatings, surface dealloying, and surface topography modifications for improving osteointegration have been investigated. However, studies have not yet established which of the surface property is more influential. In this study, titanium surfaces were treated hydrothermally with sodium hydroxide and sulfuric acid separately. This treatment led to the development of two unique surface topography at nanoscale. These modified surfaces were characterized for surface morphology, wettability, chemistry, and crystallinity. Cytotoxicity, cell adhesion, proliferation, morphology, and differentiation of adipose derived stem cells on modified surfaces was investigated. The results indicate that wettability does influence initial cell adhesion. However, the surface morphology can play major role in cell spreading, proliferation and differentiation. The results indicate that titanium surfaces treated hydrothermally with sodium hydroxide led to a nanoporous architecture that promoted appropriate cell interaction with the surface promoting osteoblastic lineage.


Assuntos
Osteogênese , Titânio , Adesão Celular , Diferenciação Celular , Proliferação de Células , Osseointegração , Osteoblastos , Células-Tronco , Propriedades de Superfície , Titânio/farmacologia
8.
Mater Sci Eng C Mater Biol Appl ; 128: 112349, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474898

RESUMO

Concise, low-cost preparation of titanium alloy implants with high cell proliferation and osteogenic differentiation is urgently needed. Nanosecond laser ablation of titanium alloy has the advantages of short processing time, less pollution, and non-contact. In this research, we adopt a nanosecond UV laser to process the closed groove and cross groove titanium alloys with length to width ratio of 1:1, 2.5:1, 4:1, and 6:1. The surface morphology, surface roughness, phase, element distribution, surface chemistry, and wettability were characterized. The effect of the patterned surface's properties on the adhesion, proliferation, and osteogenic differentiation of stem cells was studied. The results show the laser-ablated lattice structure's surface energy can increase rapidly in the natural environment. The cell adhesion of stem cells on a lattice structure with low roughness and high surface energy is optimal. The element concentration at the ablated edges is higher than at the bottom under Marangoni and surface tension. Stem cells preferentially adhere to the ablated edges with high roughness, element concentration, and hardness. Cell differentiation is chiefly affected by patterning structure. On the surface of the boss structure with a length to width ratio of 2.5:1, the proportion of cell length to diameter is about 2.5, and the cell area is greater. The osteogenic differentiation of cells is the highest on the surface.


Assuntos
Ligas , Titânio , Diferenciação Celular , Proliferação de Células , Lasers , Osteoblastos , Osteogênese , Propriedades de Superfície , Titânio/farmacologia
9.
Mater Sci Eng C Mater Biol Appl ; 128: 112353, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474901

RESUMO

Cobalt-chromium (CoCr)-based alloys have emerged as an interesting biomaterial within biomedical field, mainly considering their biocompatibility, resistance to corrosion and absence of magnetism; however, its effect on cell metabolism is barely known and this prompted us better evaluating whether CoCr-enriched medium affects the metabolism of both osteoblast and endothelial cells, and also if there is a coupling between them. This is also considered here the already-known effect of Cobalt (Co) as a hypoxic element. Firstly, discs of CoCr [subjecting (W) or not (Wo) to dual acid-etched (DAE)] were incubated into FBS-free cell culture medium up to 24 h (37 °C). This CoCr-enriched medium was further used to treat shear-stressed endothelial cells cultures up to 72 h. Thereafter, the conditioned medium containing metabolites of shear-stressed endothelial cells in response to CoCr-enriched medium was further used to subject osteoblast's cultures, when the samples were properly harvested to allow the analysis of the molecular issues. Our data shows that CoCr-enriched medium contains 1.5 ng-2.0 ng/mL of Co, which was captured by endothelial cells and osteoblasts in about 30% in amount and it seems modulate their metabolic pathways: shear-stressed endothelial cells expressed higher profile of HIF1α, VEGF and nNOS genes, while their global profile of protein carbonylation was lower than the control cultures, suggesting lower oxidative stress commitment. Additionally, osteoblasts responding to metabolites of CoCr-challenged endothelial cells show dynamic expression of marker genes in osteogenic differentiation, with alkaline phosphatase (ALP), osteocalcin, and bone sialoprotein (BSP) genes being significantly increased. Additionally, tensional shear-stress forces decrease the stimulus for ColA1gene expression in osteoblasts responding to endothelial cells metabolites, as well as modifying the extracellular matrix remodeling related genes. Analyzing the activities of matrix metalloproteinases (MMPs), the data shows that shear-stressed endothelial cells metabolites increase the activities of both MMP9 and MMP2 in osteoblasts. Altogether, our data shows for the first time that shear-stressed endothelial metabolites responding to CoCr discs contribute to osteogenic phenotype in vitro, and this predicts an active crosstalk between angiogenesis and osteogenesis during osseointegration of CoCr alloy and bone healing, maybe guided by the Co-induced hypoxic condition.


Assuntos
Cromo , Cobalto , Diferenciação Celular , Cobalto/farmacologia , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais , Osteoblastos , Osteogênese
10.
Shanghai Kou Qiang Yi Xue ; 30(3): 232-236, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476436

RESUMO

PURPOSE: To explore whether resveratrol dependents on the production of suppressor of cytokine signaling suppressor 3 (SOCS-3) in inhibiting mRNA production of macrophage inflammatory protein-2 (MIP-2) in osteoblasts induced by lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e). METHODS: MC3T3-E1 cells were treated with different concentrations of resveratrol (0, 5, 10 and 20 µmol/L) and 20 µmol/L resveratrol for different time( 0, 10, 30, 60, 120 and 180 min). The expression of SOCS-3 protein was detected by Western blot. MC3T3-E1 cells were transfected with mouse SOCS3 siRNA (si-SOCS-3) and control siRNA(si-control). Reverse transcription real-time PCR(real-time RT-PCR) and Western blot was used to detect the silencing efficiency of SOCS-3. Cells were stimulated by 20 µg/mL P.e-LPS for 24 h after transfection, in the absence or presence of 20 µmol/L resveratrol for 1 h , and the changes of MIP-2 mRNA were determined by real-time RT-PCR. Statistical analysis was performed using one-way ANOVA and Dunnett t test with SPSS 13.0 software package. RESULTS: Treatment of MC3T3-El cells with different concentrations of resveratrol caused a significant increase in SOCS-3 protein expression in a dose-dependent manner. During the observation time of 180 min, SOCS-3 protein expression was the highest at 20 µmol/L resveratrol-treated osteoblasts for 60 min. The silencing efficiency of SOCS-3 mRNA was 63.7%. Transfection with SOCS-3 siRNA increased MIP-2 mRNA expression in LPS-stimulated MC3T3-E1 cells and negated the inhibitory effects of resveratrol on LPS-induced MIP-2 mRNA expression(P<0.05). CONCLUSIONS: Resveratrol inhibits the expression of MIP-2 mRNA in osteoblasts induced by P.e-LPS by up-regulating the expression of SOCS-3 protein.


Assuntos
Lipopolissacarídeos , Porphyromonas endodontalis , Animais , Lipopolissacarídeos/farmacologia , Camundongos , Osteoblastos , RNA Mensageiro , Resveratrol/farmacologia
11.
Head Face Med ; 17(1): 37, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479596

RESUMO

BACKGROUND: Cold atmospheric plasma (CAP) has recently been identified as a novel therapeutic strategy for supporting processes of wound healing. Since CAP is additionally known to kill malignant cells, our study intends to determine the influence of CAP on crucial molecules involved in the molecular mechanism of apoptosis in osteoblast-like cells. METHODS: Human osteoblast-like cells were CAP-treated for 30 and 60 s. CAP effects on critical factors related to apoptosis were studied at transcriptional and protein level using real time-PCR, immunofluorescence staining and western blot. Phalloidin / DAPI staining was used for analyzing the cell morphology. In addition, apoptotic outcomes of CAP were displayed using flow cytometry analysis. For studying intracellular signaling pathways, MAP kinase MEK 1/2 and PI3K were blocked. Finally, the effects of CAP on caspase-3 activity were examined using a caspase-3 assay. RESULTS: CAP treatment resulted in a significant downregulation of p53 and apoptotic protease activating factor (APAF)-1, caspase (CASP)9, CASP3, BCL2 Antagonist/Killer (BAK)1, and B-Cell Lymphoma (BCL)2 mRNA expression at 1 d. An inhibitory effect of CAP on apoptotic genes was also shown under inflammatory and apoptotic conditions. Nuclear translocation of p53 was determined in CAP treated cells at the early and late stage, after 15 min, 30 min, and 1 h. p53 and APAF-1 protein levels were reduced at 1 d, visualized by immunofluorescence and western blot, respectively. Moreover, a morphological cytoskeleton modification was observed after CAP treatment at 1 d. Further, both CAP-treated and untreated (control) cells remained equally vital as detected by flow cytometry analysis. Interestingly, CAP-associated downregulation of CASP9 and CASP3 mRNA gene expression was also visible after blocking MAP kinase and PI3K. Finally, CAP led to a decrease in CASP3 activity in osteoblast-like cells under normal and apoptotic conditions. CONCLUSIONS: Our in vitro-study demonstrated, that CAP decreases apoptosis related molecules in osteoblast-like cells, underlining a beneficial effect on hard-tissue cells.


Assuntos
Gases em Plasma , Apoptose , Humanos , Osteoblastos , Gases em Plasma/farmacologia , Transdução de Sinais , Cicatrização
12.
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
13.
Life Sci ; 284: 119938, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506837

RESUMO

AIMS: The relationship between stress to endoplasmic reticulum (ER) and periodontitis has been known, and ER stress induced by Porphyromonas gingivalis results in the loss of alveolar bone. Salubrinal is a small synthetic compound and attenuates ER stress through inhibition of de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). In this study, we examined whether salubrinal attenuates periodontitis in a mouse model of experimental periodontal disease. MATERIALS AND METHODS: We evaluated loss of alveolar bone and attachment levels in periodontium using micro-computed tomography (µCT) and hematoxylin-eosin (HE) staining, respectively. Furthermore, we measured osteoclast numbers using tartrate-resistant acid phosphatase (TRAP) staining and osteoblast numbers using HE staining for bone resorption and for bone formation, respectively. To examine the inhibitory effects of salubrinal against pro-inflammatory cytokines, we measured TNF-α and IL1-ß score in periodontium using immunohistostaining. KEY FINDINGS: The results revealed that salubrinal suppressed loss of alveolar bone and attachment levels in periodontium induced by periodontitis. It decreased osteoclast numbers and increased osteoblasts. It also suppressed the expression levels of TNF-α in periodontium. SIGNIFICANCE: These results show that salubrinal alleviates periodontitis through suppression of alveolar bone resorption and the pro-inflammatory cytokine, and promotion of the bone formation. Since salubrinal has been shown to have these beneficial effects for periodontal disease, it may provide a novel therapeutic possibility for the disease.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Cinamatos/uso terapêutico , Tioureia/análogos & derivados , Perda do Osso Alveolar/complicações , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/patologia , Animais , Contagem de Células , Cinamatos/administração & dosagem , Cinamatos/farmacologia , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Interleucina-1beta/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Periodontite/complicações , Periodontite/tratamento farmacológico , Periodontite/patologia , Tioureia/administração & dosagem , Tioureia/farmacologia , Tioureia/uso terapêutico , Fator de Transcrição CHOP/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Microtomografia por Raio-X
14.
Cell Prolif ; 54(10): e13113, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34498342

RESUMO

OBJECTIVES: In recent years, long non-coding RNAs (lncRNAs) have been found to play a role in the occurrence, progression and prognosis of chronic musculoskeletal disorders. DESIGN AND METHODS: Literature exploring on PubMed was conducted using the combination of keywords 'LncRNA' and each of the following: 'osteoarthritis', 'rheumatoid arthritis', 'osteoporosis', 'osteogenesis', 'osteoclastogenesis', 'gout arthritis', 'Kashin-Beck disease', 'ankylosing spondylitis', 'cervical spondylotic myelopathy', 'intervertebral disc degeneration', 'human muscle disease' and 'muscle hypertrophy and atrophy'. For each disorder, we focused on the publications in the last five years (5/1/2016-2021/5/1, except for Kashin-Beck disease). Finally, we excluded publications that had been reported in reviews of various musculoskeletal disorders during the last three years. Here, we summarized the progress of research on the role of lncRNA in multiple pathological processes during musculoskeletal disorders. RESULTS: LncRNAs play a crucial role in regulating downstream gene expression and maintaining function and homeostasis of cells, especially in chondrocytes, synovial cells, osteoblasts, osteoclasts and skeletal muscle cells. CONCLUSIONS: Understanding the mechanisms of lncRNAs in musculoskeletal disorders may provide promising strategies for clinical practice.


Assuntos
Doenças Musculoesqueléticas/genética , RNA Longo não Codificante/genética , Animais , Condrócitos/fisiologia , Progressão da Doença , Homeostase/genética , Humanos , Doenças Musculoesqueléticas/patologia , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Prognóstico , Sinoviócitos/fisiologia
15.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502045

RESUMO

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.


Assuntos
Fibronectinas/metabolismo , Homeostase , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Animais , Humanos
16.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502056

RESUMO

Skeletal tissue involves systemic adipose tissue metabolism and energy expenditure. MicroRNA signaling controls high-fat diet (HFD)-induced bone and fat homeostasis dysregulation remains uncertain. This study revealed that transgenic overexpression of miR-29a under control of osteocalcin promoter in osteoblasts (miR-29aTg) attenuated HFD-mediated body overweight, hyperglycemia, and hypercholesterolemia. HFD-fed miR-29aTg mice showed less bone mass loss, fatty marrow, and visceral fat mass together with increased subscapular brown fat mass than HFD-fed wild-type mice. HFD-induced O2 underconsumption, respiratory quotient repression, and heat underproduction were attenuated in miR-29aTg mice. In vitro, miR-29a overexpression repressed transcriptomic landscapes of the adipocytokine signaling pathway, fatty acid metabolism, and lipid transport, etc., of bone marrow mesenchymal progenitor cells. Forced miR-29a expression promoted osteogenic differentiation but inhibited adipocyte formation. miR-29a signaling promoted brown/beige adipocyte markers Ucp-1, Pgc-1α, P2rx5, and Pat2 expression and inhibited white adipocyte markers Tcf21 and Hoxc9 expression. The microRNA also reduced peroxisome formation and leptin expression during adipocyte formation and downregulated HFD-induced leptin expression in bone tissue. Taken together, miR-29a controlled leptin signaling and brown/beige adipocyte formation of osteogenic progenitor cells to preserve bone anabolism, which reversed HFD-induced energy underutilization and visceral fat overproduction. This study sheds light on a new molecular mechanism by which bone integrity counteracts HFD-induced whole-body fat overproduction.


Assuntos
Gordura Intra-Abdominal/metabolismo , Leptina/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoporose/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular , Dieta Hiperlipídica/efeitos adversos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Leptina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Osteoblastos/citologia , Osteoporose/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Peroxissomos/metabolismo , Receptores Purinérgicos P2X5/genética , Receptores Purinérgicos P2X5/metabolismo , Simportadores/genética , Simportadores/metabolismo , Termogênese , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
17.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576150

RESUMO

Several decontamination methods for removing biofilm from implant surfaces during surgical peri-implantitis treatment have been reported, including the intraoperative usage of chlorhexidine (CHX)-based antiseptics. There is a lack of information on possible adverse effects on bone healing. The study aimed to examine the impact of three CHX-based mouthwashes on osteoblast-like cells (SaOS-2) in vitro. Cells were cultured for three days in 96-well binding plates. Each well was randomly treated for either 30, 60 or 120 s with 0.05% CHX combined with 0.05% cetylpyridinium chloride (CPC), 0.1% CHX, 0.2% CHX or sterile saline (NaCl) as control. Cell viability, cytotoxicity and apoptosis were assessed at day 0, 3 and 6. Cell viability resulted in being higher in the control group at all time points. At day 0, the CHX 0.2 group showed significantly higher cytotoxicity values compared to CHX 0.1 (30 s), CHX + CPC (30 s, 60 s and 120 s) and control (60 s and 120 s), while no significant differences were identified between CHX + CPC and both CHX 0.1 and NaCl groups. All test mouthwashes were found to induce apoptosis to a lower extent compared to control. Results indicate that 0.2% CHX presented the highest cytotoxic effect. Therefore, its intraoperative use should be carefully considered.


Assuntos
Clorexidina/farmacologia , Antissépticos Bucais/farmacologia , Osteoblastos/citologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Osteoblastos/efeitos dos fármacos
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(8): 1277-1282, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34549722

RESUMO

OBJECTIVE: To prepare the human bone morphogenetic protein-2(hBMP-2)/human insulin-like growth factor-1(hIGF-1)coating titanium(Ti)and assess its performance as a dental implant material. METHODS: hBMP-2 and hIGF-1 were coated to the smooth surface of a Ti plate, and its efficacy for promoting bone formation and bone integration was compared with a pristine Ti plate.The surface characteristics of the metal samples were evaluated using scanning electron microscope (SEM) and by contact angle measurement.MG63 cells were seeded on the surface of the Ti plates, and MTT assay and alizarin red staining was used to examine the cell proliferation and formation of calcified nodules, respectively.Alkaline phosphatase (ALP)secretion of the cells was examined with ELISA, and cellular expressions of osteocalcin and osteopontin were detected with Western blotting for assessing osteogenesis. RESULTS: SEM examination showed that the surface of Ti with hBMP-2 and hIGF-1 coating presented with a radial pattern resembling snowflakes.The contact angles of non-coated Ti, hBMP-2-coated Ti, hIGF-1-coated, and hBMP-2/-hIGF-1-coated Ti samples were 83.2°, 54°, 56° and 54°, respectively.Compared with the non-coated Ti plate, the surface-modified Ti samples showed a significantly smaller contact angle (P=0.032, 0.029, and 0.028), indicating a good hydrophilicity of the samples.MTT assay showed that MG63 cells grew well on the surface of the coated Ti plates.The hBMP-2/IGF-1 coating significantly induced cellular secretion of ALP(P=0.021, 0.014)and obviously promoted osteogenesis of MG63 cells (P < 0.05).Western blotting results showed that hBMP-2/IGF-1 coating significantly enhanced the expressions of osteocalcin and osteopontin in the seeded cells (P < 0.05). CONCLUSION: hBMP-2 and hIGF-1 coating of Ti material can promote osteogenesis of the cells seeded on its surface to improve the performance of such Ti material as dental implants.


Assuntos
Osteogênese , Titânio , Materiais Revestidos Biocompatíveis , Humanos , Osteoblastos , Osteocalcina , Próteses e Implantes , Propriedades de Superfície
19.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502120

RESUMO

Diabetes mellitus is a main risk factor for delayed fracture healing and fracture non-unions. Successful fracture healing requires stimuli from different immune cells, known to be affected in diabetics. Especially, application of mononuclear cells has been proposed to promote wound and fracture healing. Thus, aim was to investigate the effect of pre-/diabetic conditions on mononuclear cell functions essential to promote osteoprogenitor cell function. We here show that pre-/diabetic conditions suppress the expression of chemokines, e.g., CCL2 and CCL8 in osteoprogenitor cells. The associated MCP-1 and MCP-2 were significantly reduced in serum of diabetics. Both MCPs chemoattract mononuclear THP-1 cells. Migration of these cells is suppressed under hyperglycemic conditions, proposing that less mononuclear cells invade the site of fracture in diabetics. Further, we show that the composition of cytokines secreted by mononuclear cells strongly differ between diabetics and controls. Similar is seen in THP-1 cells cultured under hyperinsulinemia or hyperglycemia. The altered secretome reduces the positive effect of the THP-1 cell conditioned medium on migration of osteoprogenitor cells. In summary, our data support that factors secreted by mononuclear cells may support fracture healing by promoting migration of osteoprogenitor cells but suggest that this effect might be reduced in diabetics.


Assuntos
Meios de Cultivo Condicionados/metabolismo , Diabetes Mellitus/metabolismo , Consolidação da Fratura , Monócitos/metabolismo , Animais , Biomarcadores , Movimento Celular , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL8/metabolismo , Quimiocinas/metabolismo , Quimiotaxia de Leucócito/imunologia , Humanos , Hiperglicemia/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Sistema de Sinalização das MAP Quinases , Monócitos/imunologia , Osteoblastos/metabolismo , Osteogênese , Células THP-1
20.
FASEB J ; 35(10): e21851, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34547121

RESUMO

It has been known that moderate mechanical loading, like that caused by exercise, promotes bone formation. However, its underlying mechanisms remain elusive. Here we showed that moderate running dramatically improved trabecular bone in mice tibias with an increase in bone volume fraction and trabecular number and a decrease in trabecular pattern factor. Results of immunohistochemical and histochemical staining revealed that moderate running mainly increased the number of osteoblasts but had no effect on osteoclasts. In addition, we observed a dramatic increase in the number of colony forming unit-fibroblast in endosteal bone marrow and the percentage of CD45- Leptin receptor+ (CD45- LepR+ ) endosteal mesenchymal progenitors. Bioinformatics analysis of the transcriptional data from gene expression omnibus (GEO) database identified chemokine c-c-motif ligands (CCL2) as a critical candidate induced by mechanical loading. Interestingly, we found that CCL2 was up-regulated mainly in osteoblastic cells in the tibia of mice after moderate running. Further, we found that mechanical loading up-regulated the expression of CCL2 by activating ERK1/2 pathway, thereby stimulating migration of endosteal progenitors. Finally, neutralizing CCL2 abolished the recruitment of endosteal progenitors and the increased bone formation in mice after 4 weeks running. These results therefore uncover an unknown connection between osteoblasts and endosteal progenitors recruited in the increased bone formation induced by mechanical loading.


Assuntos
Osso Esponjoso/citologia , Quimiocina CCL2/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteogênese , Condicionamento Físico Animal , Animais , Osso Esponjoso/metabolismo , Movimento Celular , Quimiocina CCL2/genética , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo
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