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1.
Article in Chinese | WPRIM | ID: wpr-879427

ABSTRACT

Osteoporosis is one of the common clinical orthopedic diseases, which can lead to a variety of complications. There are many pathogenic factors in this disease. The latest research found that ATP6V1H is a new gene leading to the occurrence of osteoporosis, and it is likely to become a new target for the future drug treatment of osteoporosis.This paper introduces the biological structure and characteristics of H subunit, summed up the human body caused by loss of ATP6V1H and animal models such as zebrafish, mice bone loss and osteoporosis symptom such as related research reports of the loss, from osteoclast, osteoblast and marrow stromal cell level and the connection between the various subunits further expounds the H subunit regulate bone dynamic balance of mechanism, to explore ATP6V1H in bone developmentand bone related diseases has laid a solid foundation, also provide new ideas for clinical treatment of osteoporosis.


Subject(s)
Animals , Bone and Bones , Mice , Osteoblasts , Osteoclasts , Osteoporosis/genetics , Zebrafish
2.
Article in Chinese | WPRIM | ID: wpr-878434

ABSTRACT

Bone invasion by oral cancer is a common clinical problem, which affects the choice of treatment and predicts a poor prognosis. Unfortunately, the molecular mechanism of this phenomenon has not been fully elucidated. Current studies have revealed that oral cancer cells modulate the formation and function of osteoclasts through the expression of a series of signal molecules. Many signal pathways are involved in this process, of which receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin signaling pathway attracted much attention. In this review, we introduce recent progress in molecular mechanisms of bone invasion by oral cancer.


Subject(s)
Bone Resorption , Bone and Bones , Humans , Mouth Neoplasms , Osteoclasts , Osteoprotegerin , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B
3.
Article in Chinese | WPRIM | ID: wpr-878423

ABSTRACT

OBJECTIVES@#This study aimed to explore the changes in the expression of the characteristic transcription factor retinoid related orphan receptor γt (RORγt) and the cytokine interleukin-17 (IL-17) of T helper cell 17 (Th17) in the pressure side of the periodontal tissue of rats under different orthodontic forces. Their effects on the expression of osteoprotegerin (OPG) and the quantity of osteoclast (OC) were also explored. The role of Th17 cell in alveolar bone remodeling under different forces was preliminarily investigated.@*METHODS@#A total of 108 rats were chosen and randomly divided into three groups. Mesial forces of 0, 50, and 100 g were loaded on the maxillary first molar in the three groups. The rats were executed at 0, 1, 3, 5, 7, and 14 days. The expression of RORγt mRNA was quantified by real-time quantitative polymerase chain reaction. The expression of IL-17 protein was quantified by enzyme linked immunosorbent assay. The expression levels of RORγt and OPG proteins were quantified, and the quantity of OC was counted via immunohistochemistry.@*RESULTS@#The expression levels of RORγt and IL-17 and the quantity of OC increased first and then decreased in the 50 and 100 g groups, and the peak values of the two groups were on days 5 and 7, respectively. The expression levels in the 50 g group basically recovered to normal level on day 14, while that in the 100 g group remained at a high level. The expression levels in the 50 g group were higher than those in the 0 g group and lower than those in the 100 g group. The expression of OPG in the 50 g group decreased first, then increased, and finally decreased. It basically recovered to normal level on day 14. The expression of OPG in the 100 g group decreased first and then increased. It remained at a high level on day 14. The expression in the 50 g group was significantly higher than that in the 0 g group on day 7, while the expression in the 100 g group was significantly higher than that in the 0 g group on day 14.@*CONCLUSIONS@#RORγt, IL-17, and OPG were expressed regularly over time under different orthodontic forces, indicating that Th17 participated in the process of bone resorption on the pressure side of periodontal tissue by secreting IL-17.


Subject(s)
Animals , Bone Resorption , Cytokines , Interleukin-17 , Molar , Nuclear Receptor Subfamily 1, Group F, Member 3 , Osteoclasts , Osteoprotegerin , Rats , Th17 Cells , Tooth Movement Techniques
4.
Article in Chinese | WPRIM | ID: wpr-880824

ABSTRACT

OBJECTIVE@#To investigate the regulatory role of long non-coding RNA Kcnq1ot1 in osteoclast differentiation, osteogenic differentiation and osteoporosis.@*METHODS@#The expression of lnc-Kcnq1ot1, Bglap, Runx2, Alp, Bsp, Nfatc1, Mmp9, Ctsk and Oscar were detected by real-time quantitative PCR (qRT-PCR) in the femoral bones from mouse models of postmenopausal osteoporosis (ovariectomized mice, @*RESULTS@#The expression of lnc-Kcnq1ot1 was significantly upregulated during osteoblast differentiation but downregulated in the bone tissues of osteoporotic mice and during osteoclast differentiation (@*CONCLUSIONS@#Our data demonstrate that lnc-Kcnq1ot1 promotes osteogenic differentiation and alleviates osteoclast differentiation, suggesting the potential of lnc-Kcnq1ot1 as a therapeutic target against osteoporosis.


Subject(s)
Animals , Cell Differentiation , Cells, Cultured , Mice , Osteoblasts , Osteoclasts , Osteogenesis
5.
Article in English | WPRIM | ID: wpr-879968

ABSTRACT

To investigate the effects of interleukin (IL)-17-mediated autophagy on the TNF receptor associated factor (TRAF6)/extracellular signal-regulated kinase (ERK)/p38 pathway and osteoclast differentiation. Mouse bone marrow-derived macrophages (BMM) were cultured with a medium containing 30 ng/mL macrophage colony stimulating factor and 50 ng/mL receptor activator of nuclear factor-kappa B ligard (RANKL), and IL-17 (0.01, 0.1, 1.0, 10 ng/mL) was added for intervention (IL-17 group). Tartrate-resistant acid phosphatase (TRAP) staining was used to observe TRAP positive multinucleated cells; phalloidin fluorescent staining was used to detect actin ring circumference; toluidine blue staining was used to analyze bone resorption lacuna formation. To further examine the mechanism of the effect of IL-17-mediated autophagy on the differentiation of osteoclasts, the control group used RANKL medium to culture mouse macrophage RAW264.7 cells, while the IL-17 group was treated with IL-17 (0.01, 0.1, 1.0, /mL). Western blot was used to detect the expression of autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) and osteoclast-related proteins c-fos and nuclear factor of activated T cell 1 (NFATc1) after treatment with different concentrations of IL-17. The expression of LC3, NFATc1, TRAF6/ERK/p38 signaling pathway related proteins were detected in IL-17 and autophagy inhibitor 3-MA group. The number of TRAP positive multinucleated cells, the circumference of the actin ring and the area of bone resorption lacuna in IL-17 group treated with IL-17 (0.01, 0.1, were significantly higher than those in the control group. In IL-17 treated RAW264.7 cells, the expression of c-fos, NFATc1, Beclin-1, LC3, TRAF6, p-ERK, and p-p38 was all significantly up-regulated (all 0.05). After treatment with the autophagy inhibitor 3-MA, the expression levels of LC3, NFATc1, TRAF6, p-ERK, and p-p38 all decreased significantly (all 0.05). IL-17 can promote the expression of autophagy proteins and enhance the differentiation ability of osteoclast precursor cells, and the TRAF6/ERK/p38 signaling pathway may be involved in this process.


Subject(s)
Animals , Autophagy , Bone Resorption , Cell Differentiation , Extracellular Signal-Regulated MAP Kinases , Interleukin-17 , Mice , NFATC Transcription Factors/metabolism , Osteoclasts/metabolism , RANK Ligand/metabolism , TNF Receptor-Associated Factor 6
6.
J. appl. oral sci ; 29: e20200791, 2021. tab, graf
Article in English | LILACS | ID: biblio-1250185

ABSTRACT

Abstract Background: IGF-1 may be an important factor in bone remodeling, but its mechanism of action on osteoclasts during orthodontic tooth movement is complex and unclear. Methodology: The closed-coil spring was placed between the left maxillary first molar and upper incisors with a force of 50 g to establish an orthodontic movement model. Eighty SD rats were randomized to receive phosphate buffer saline or 400 ng rhIGF-1 in the lateral buccal mucosa of the left maxillary first molar every two days. Tissue sections were stained for tartrate-resistant acidic phosphatase (TRAP), the number of TRAP-positive cells was estimated and tooth movement measured. Results: The rhIGF-1 group exhibited evidential bone resorption and lacuna appeared on the alveolar bone compared to the control group. Moreover, the number of osteoclasts in compression side of the periodontal ligament in the rhIGF-1 group peaked at day 4 (11.37±0.95 compared to 5.28±0.47 in the control group) after the orthodontic force was applied and was significantly higher than that of the control group (p<0.01). Furthermore, the distance of tooth movement in the rhIGF-1 group was significantly larger than that of the control group from day 4 to day 14 (p<0.01), suggesting that rhIGF-1 accelerated orthodontic tooth movement. Conclusion: Our study has showed that rhIGF-1 could stimulate the formation of osteoclasts in the periodontal ligament, and accelerate bone remodeling and orthodontic tooth movement.


Subject(s)
Humans , Animals , Rats , Osteoclasts , Tooth Movement Techniques , Periodontal Ligament , Insulin-Like Growth Factor I , Bone Remodeling , Rats, Sprague-Dawley
8.
Actual. osteol ; 16(2): [132]-[140], mayo.-ago. 2020. ilus
Article in Spanish | LILACS | ID: biblio-1129806

ABSTRACT

La oxitocina (OXT) como la arginina-vasopresina (AVP) son dos hormonas primitivas secretadas por la hipófisis posterior. Sus receptores están mucho más ampliamente distribuidos en el organismo de lo que se pensaba originalmente, incluido el hueso. En los estudios preclínicos, la OXT ha mostrado ser anabólica para el hueso, promoviendo la osteogénesis sobre la adipogénesis y favoreciendo la actividad osteoblástica sobre la osteoclástica. Tanto los osteoblastos como los osteoclastos tienen receptores para la OXT, y los efectos de los estrógenos sobre la masa ósea en ratones está mediada por lo menos en parte por la OXT. El mecanismo preciso por el cual la activación de los receptores de oxitocina (OXTR) se traduce en un incremento de la formación ósea permanece poco claro. La AVP también podría afectar el esqueleto en forma directa. Dos de los receptores de la AVP, V1a y V2 están expresados en osteoblastos y osteoclastos. La inyección de AVP en ratones de tipo salvaje aumenta la formación osteoclastos que producen resorción y reduce los osteoblastos formadores de hueso. En forma opuesta, la exposición de precursores osteoblásticos a antagonistas de los receptores V1a o V2, incrementan la osteoblastogénesis, como también lo hace la deleción genética del receptor V1a. (AU)


Both oxytocin (OXT) and argininevasopressin (AVP) are primitive hormones secreted by the posterior pituitary gland. OXT receptors are much more widely distributed in the body than originally thought, including in bone. In preclinical studies, OXT has been shown to be anabolic for bone, promoting osteogenesis over adipogenesis and favoring osteoblastic over osteoclastic activity. Both osteoblasts and osteoclasts have receptors for OXT, and the effects of estrogen on bone mass in mice is mediated at least in part by OXT. The precise mechanism by which the activation of oxytocin receptors (OXTRs) results in an increase in bone formation remains unclear. AVP could also have direct actions on the skeleton. The two AVP receptors, V1a and V2, are expressed in osteoblasts and osteoclasts. Injection of AVP in wild-type mice increases the formation of osteoclasts increasing bone resorption, and reduces bone-forming osteoblasts. On the contrary, the exposure of osteoblastic precursors to V1a and V2 antagonists increase osteoblastogenesis, the same as the genetic deletion of the V1a receptor. (AU)


Subject(s)
Humans , Animals , Mice , Pituitary Hormones, Posterior/biosynthesis , Arginine Vasopressin/adverse effects , Oxytocin/therapeutic use , Osteoblasts/physiology , Osteoclasts/physiology , Osteogenesis , Osteoporosis/therapy , Pituitary Hormones, Posterior/physiology , Arginine Vasopressin/antagonists & inhibitors , Arginine Vasopressin/biosynthesis , Arginine Vasopressin/physiology , Arginine Vasopressin/therapeutic use , Oxytocin/biosynthesis , Oxytocin/adverse effects , Oxytocin/physiology , Signal Transduction , Bone Density , Bone Density/drug effects , Receptors, Oxytocin/biosynthesis , Receptors, Oxytocin/physiology , Estradiol/therapeutic use , Estrogens/physiology
9.
Braz. dent. j ; 31(2): 122-126, Mar.-Apr. 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1132280

ABSTRACT

Abstract Although periodontitis is one of the commonest infectious inflammatory diseases in humans, the mechanisms involved with its immunopathology remain ill understood. Numerous molecules may induce inflammation and lead to bone resorption, secondary to activation of monocytes into osteoclasts. TACE (TNF-α converting enzyme) and DC-STAMP (dendritic cell-specific transmembrane protein) appear to play a role on bone resorption since TACE induces the release of sRANKL (soluble receptor activator of nuclear factor kappa-β ligand) whereas DC-STAMP is a key factor in osteoclast induction. The present study evaluated the levels of TACE and DC-STAMP in patients with and without periodontitis. Twenty individuals were selected: 10 periodontally healthy participants undergoing gingivectomy for esthetic reasons and 10 diagnosed with periodontitis. Protein levels of such molecules in gingival tissue were established using Western blotting. Protein levels of both TACE and DC-STAMP were higher in the periodontitis group than in the control group (p<0.05; Student t-test). In conclusion, TACE and DC-STAMP protein levels are elevated in patients with periodontitis, favoring progression of bone resorption.


Resumo Apesar de a periodontite ser uma das doenças infecto inflamatórias humanas mais comuns, os mecanismos que conduzem à imunopatologia não estão bem definidos. Inúmeras moléculas induzem atividade inflamatória que levam à perda óssea. Para que haja a reabsorção óssea, células monocíticas são ativadas e se transformam em osteoclastos. As moléculas TACE (Enzima conversora de TNF-α) e DC-STAMP (Proteína transmembrana específica de célula dendrítica) parecem atuar no processo de reabsorção óssea uma vez que a TACE induz a liberação de sRANKL (ativador do receptor do fator nuclear kappa-β ligante solúvel), enquanto a DC-STAMP é um fator chave na indução dos osteoclastos. Diante disso, o presente estudo avaliou a expressão gênica das moléculas TACE e DC-STAMP em pacientes com e sem periodontite uma vez que o papel destas moléculas no curso do desenvolvimento da periodontite ainda é pouco explorado. Foram selecionados 20 indivíduos, sendo 10 com saúde periodontal e com indicação para remoção de tecido gengival por motivos estéticos e 10 pacientes com periodontite. As análises da expressão das moléculas no tecido gengival foram realizadas por meio de western blotting. Os níveis proteicos tanto de TACE quanto de DC-STAMP, foram maiores nos tecidos do grupo com periodontite em comparação aos do grupo controle (p<0.05; Student' t-test). Portanto, os dados demonstram que a expressão protéica das moléculas TACE e DC-STAMP estão elevados em pacientes com periodontite, favorecendo a progressão da reabsorção óssea nesta patologia.


Subject(s)
Humans , Periodontitis , Bone Resorption , Adaptor Proteins, Signal Transducing/metabolism , ADAM17 Protein/metabolism , Membrane Proteins/metabolism , Osteoclasts , Cell Differentiation
10.
Actual. osteol ; 16(1): 35-46, Ene - abr. 2020. graf, ilus
Article in Spanish | LILACS | ID: biblio-1139966

ABSTRACT

La erupción dental es un proceso estrictamente regulado y programado espacial y temporalmente. El objetivo del trabajo fue estudiar el efecto de la exposición prenatal a fluoruro de sodio (NaF) sobre los eventos morfológicos y celulares que ocurren en el hueso supracoronal del primer molar de crías de rata durante la etapa preeruptiva. Se emplearon crías (n=6-8 por grupo) provenientes de madres que bebieron crónicamente agua con diferentes concentraciones de F- en forma de NaF durante la gestación y lactancia: control y NaF (50 mg/L). En cortes histológicos de la mandíbula de crías de 3 y 10 días se analizaron parámetros de histomorfometría estática en la zona supracoronal de la canastilla ósea a la altura del primer molar inferior: volumen óseo trabecular [BV/TV (%)], número de osteoclastos por milímetro (N.Oc/mm) y las variables indirectas: número de trabéculas [Tb.N (1/mm)], espesor [Tb.Th (µm)] y separación trabecular [Tb.Sp (µm)]. En crías de 15 días se midió el grado de erupción [TED (µm)] del primer molar inferior. Los resultados se analizaron con el test "t" de Student considerando diferencias significativas a p<0,05. El análisis histomorfométrico demostró un incremento en el BV/TV (%) del hueso supracoronal (p<0,01) asociado con disminución del N.Oc/mm (p<0,01) en crías de 3 y 10 días expuestas prenatalmente al F-. El grado de erupción dental fue menor en animales expuestos prenatalmente al F- en comparación con los controles (p<0,01). En conclusión, los resultados observados en la mandíbula de crías expuestas durante la etapa prenatal y posnatal temprana al F- sugieren un efecto disruptivo sobre la actividad resortiva necesaria para formación del canal eruptivo. (AU)


Tooth eruption is a tightly regulated and spatially and temporally programmed process. The aim of this study was to examine the effect of prenatal NaF exposure on the morphological and cellular events that occur in the supracoronal area of bony crypt of the first rat molar during the preeruptive stage. Offspring from two groups of rats were used (6-8 per group): Control and 50 mg/L NaF. The treatment was performed during pregnancy and lactation. Suckling pups were euthanized at 3-, 10- and 15-days-old by cervical dislocation. Mandibles were removed and histologically processed to obtain buccolingual sections stained with H&E. In sections of first mandibular molar of 3- and 10-days-old pups, the following static histomorphometric parameters were evaluated: trabecular bone volume [BV/TV (%)] and number of osteoclasts (N.Oc/mm). Also, indirect parameters were obtained: trabecular number [Tb.N (1/mm)], trabecular thickness [Tb.Th (µm)], and trabecular separation [Tb.Sp (µm)]. The degree of tooth eruption [TED (µm)] was determined. Results are expressed as mean ± SE and analyzed by Student t-test. Histomorphometric analysis showed an increase in the BV/TV (%) of the bone crypt of 3- and 10- days-old pups exposed to NaF (p <0.01); this increase was associated with a decrease in the N.Oc/mm (p <0.01). TED of mandibular first molar was lower in prenatal NaF exposed group than in control group (p<0.01). In conclusion, the increased BV/TV and the lower N.Oc observed in the bone crypt of 3- and 10- days-old pups from mothers treated with NaF suggested a disruptive effect triggered by F- on the formation events of the eruptive pathway in the offspring. (AU)


Subject(s)
Humans , Animals , Male , Female , Infant , Child, Preschool , Rats , Sodium Fluoride/adverse effects , Tooth Eruption , Osteoclasts/cytology , Prenatal Exposure Delayed Effects , Sodium Fluoride/administration & dosage , Sodium Fluoride/metabolism , Sodium Fluoride/urine , Sodium Fluoride/chemical synthesis , Rats, Wistar , Mandible/anatomy & histology , Molar/growth & development , Fluorosis, Dental/diagnosis
11.
Chinese Journal of Traumatology ; (6): 314-318, 2020.
Article in English | WPRIM | ID: wpr-879643

ABSTRACT

In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bone and Bones/metabolism , Cellular Microenvironment , Humans , Immune System/immunology , Lymphocyte Subsets/immunology , Osteitis/microbiology , Osteoblasts/physiology , Osteoclasts/physiology , Staphylococcal Infections
12.
Article in English | WPRIM | ID: wpr-811184

ABSTRACT

BACKGROUND: Rosae Multiflorae fructus (RMF), known to have anti-inflammatory and antioxidant properties, has been used as a traditional remedy for inflammatory diseases such as arthritis in Eastern Asia. However, its effect on osteoclasts, which play a crucial role in resorptive inflammatory bone diseases, is yet to be elucidated.METHODS: The effect of extract of RMF (RMF-E) on receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis was examined by tartrate-resistant acid phosphatase (TRAP) staining, real-time polymerase chain reaction and western blot analysis. In addition, RANKL-induced Ca2⁺-oscillation was also investigated.RESULTS: RMF-E remarkably inhibited TRAP+-osteoclast and resorptive pit formation in a dose-dependent manner. In addition, the expression of c-Fos and nuclear factor of activated T-cells cytoplasmic, known as pivotal transcription factors for osteoclast formation in vitro and in vivo, and that of the osteoclast differentiation markers such as Acp5, Oscar, CtsK, Atp6v0d2, Tm7sf4, and Nfatc1 were significantly decreased by RMF-E treatment during osteoclastogenesis. The inhibitory effect of RMF-E on RANKL-induced osteoclastogenesis was caused by the suppression of p38 mitogen-activated protein kinase activation, and RANKL-induced Ca2⁺-oscillation removal via inactivation of Bruton's tyrosine kinase (BTK), and subsequently phospholipase C-γ2.CONCLUSIONS: RMF-E negatively regulates osteoclast differentiation and formation. These findings suggest the possibility of RMF-E as a traditional therapeutic agent against osteoclast-related bone disorders such as osteoporosis, rheumatoid arthritis, and periodontitis.


Subject(s)
Acid Phosphatase , Antigens, Differentiation , Arthritis , Arthritis, Rheumatoid , Blotting, Western , Bone Diseases , Calcium Signaling , Cytoplasm , Far East , In Vitro Techniques , Osteoclasts , Osteogenesis , Osteoporosis , Periodontitis , Phospholipases , Protein Kinases , Protein-Tyrosine Kinases , Real-Time Polymerase Chain Reaction , Rosa , T-Lymphocytes , Transcription Factors
13.
Article in English | WPRIM | ID: wpr-810950

ABSTRACT

BACKGROUND: Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.METHODS: RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.RESULTS: Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.CONCLUSION: RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.


Subject(s)
Arthritis, Rheumatoid , Cholecalciferol , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Follow-Up Studies , Hand , Humans , In Vitro Techniques , Interleukin-17 , Interleukin-6 , Interleukins , Osteoclasts , Retrospective Studies , Vitamin D , Vitamins , Wrist
14.
Article in English | WPRIM | ID: wpr-828964

ABSTRACT

Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement. However, the key regulatory molecules involved in osteoclastogenesis during this process remain unclear. Long noncoding RNAs (lncRNAs) are a newly identified class of functional RNAs that regulate cellular processes, such as gene expression and translation regulation. Recently, lncRNAs have been reported to be involved in osteogenesis and bone formation. However, as the most abundant noncoding RNAs in vivo, the potential regulatory role of lncRNAs in osteoclast formation and bone resorption urgently needs to be clarified. We recently found that the lncRNA Nron (long noncoding RNA repressor of the nuclear factor of activated T cells) is highly expressed in osteoclast precursors. Nron is downregulated during osteoclastogenesis and bone ageing. To further determine whether Nron regulates osteoclast activity during orthodontic treatment, osteoclastic Nron transgenic (Nron cTG) and osteoclastic knockout (Nron CKO) mouse models were generated. When Nron was overexpressed, the orthodontic tooth movement rate was reduced. In addition, the number of osteoclasts decreased, and the activity of osteoclasts was inhibited. Mechanistically, Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation. In contrast, by deleting Nron specifically in osteoclasts, tooth movement speed increased in Nron CKO mice. These results indicate that lncRNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.


Subject(s)
Animals , Bone Resorption , Genetics , Mice , Mice, Inbred C57BL , Osteoclasts , Osteogenesis , RANK Ligand , RNA, Long Noncoding , Genetics
15.
Article in Chinese | WPRIM | ID: wpr-828102

ABSTRACT

OBJECTIVE@#To explore the effect of advanced glycation end products (AGEs) on osteoclasts at different stages of differentiation.@*METHODS@#Raw264.7 cells cultured were induced for osteoclastogenesis using RANKL, and the stages of differentiation of the osteoclasts were determined with TRAP staining. The cells were then randomly divided into control group, early-stage AGEs intervention group and late-stage AGEs intervention group. The viability of the cells after AGEs treatment was assessed using CCK-8 method. The cells were examined after the induction for osteoclastogenesis using TRAP staining, and the expression levels of RANK, NFATC-1, TRAF-6, TRAP and CTSK mRNAs were tested with RT-PCR; the expressions of CTSK and RANK proteins were detected using Western boltting.@*RESULTS@#We defined the initial 3 days of induction as the early stage of differentiation and the time beyond 3 days as the late stage of differentiation of Raw264.7 cells. Intervention with AGEs at 100 mg/L produced no significant effects on the viability of the cells, but AGEs suppressed the cell proliferation at a concentration exceeding 100 mg/L. The number of osteolasts in the early- and late-stage intervention groups was greater than that in the control group, but the cell count differed significantly only between the early-stage intervention group and control group ( < 0.05). The gene expressions of RANK, NFATC-1, TRAF-6, TRAP and CTSK all increased after the application of AGEs in both the early and late stages of differentiation, but the changes were significant only in the early-stage intervention group ( < 0.05). The changes in CTSK and RANK protein expressions were consistent with their mRNA expressions.@*CONCLUSIONS@#AGEs can affect the differentiation of osteoclasts differently when applied at different stages, and intervention with AGEs at the early stage produces stronger effect to promote osteoclast differentiation than its application at a late stage.


Subject(s)
Animals , Bone Resorption , Cell Differentiation , Mice , Osteoclasts , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B
16.
Article in Chinese | WPRIM | ID: wpr-878397

ABSTRACT

Strontium (Sr) is an essential trace element and widely exists in nature. It plays an important role in the in vivo regulation of bone metabolism. Sr locates below Fe in the periodic table, and its chemical structure and polarity are similar to those of Ca. It can induce bone mesenchymal stem cells to differentiate into osteoblasts by inhibiting the activity of osteoclasts and reducing bone resorption. It promotes bone formation through a series of related pathways. The mechanism of Sr regulation of bone metabolism has been extensively researched in recent years. The current study aims to investigate the mechanism of Sr and provide a theoretical basis for its clinical application.


Subject(s)
Bone Resorption , Humans , Osteoblasts , Osteoclasts , Osteogenesis , Strontium
17.
Article in English | WPRIM | ID: wpr-785339

ABSTRACT

PURPOSE: Osteitis refers to the development of new bone formation and remodeling of bone in chronic rhinosinusitis (CRS) patients; it is typically associated with eosinophilia, nasal polyps (NPs), and recalcitrant CRS. However, the roles of ossification in CRS with or without NPs remain unclear due to the lack of appropriate animal models. Thus, it is necessary to have a suitable animal model for greater advances in the understanding of CRS pathogenesis.METHODS: BALB/c mice were administered ovalbumin (OVA) and staphylococcal enterotoxin B (SEB). The numbers of osteoclasts and osteoblasts and bony changes were assessed. Micro computed tomography (micro-CT) scans were conducted to measure bone thickness. Immunofluorescence, immunohistochemistry, and quantitative polymerase chain reaction were performed to evaluate runt-related transcription factor 2 (RUNX2), osteonectin, interleukin (IL)-13, and RUNX2 downstream gene expression. Gene set enrichment analysis was performed in mucosal tissues from control and CRS patients. The effect of resveratrol was evaluated in terms of osteogenesis in a murine eosinophilic CRS NP model.RESULTS: The histopathologic changes showed markedly thickened bones with significant increase in osteoblast numbers in OVA/SEB-treated mice compared to the phosphate-buffered saline-treated mice. The structural changes in bone on micro-CT were consistent with the histopathological features. The expression of RUNX2 and IL-13 was increased by the administration of OVA/SEB and showed a positive correlation. RUNX2 expression mainly co-localized with osteoblasts. Bioinformatic analysis using human CRS transcriptome revealed that IL-13-induced bony changes via RUNX2. Treatment with resveratrol, a candidate drug against osteitis, diminished the expression of IL-13 and RUNX2, and the number of osteoblasts in OVA/SEB-treated mice.CONCLUSIONS: In the present study, we found the histopathological and radiographic evidence of osteogenesis using a previously established murine eosinophilic CRS NP model. This animal model could provide new insights into the pathophysiology of neo-osteogenesis and provide a basis for developing new therapeutics.


Subject(s)
Animals , Computational Biology , Core Binding Factor Alpha 1 Subunit , Enterotoxins , Eosinophilia , Eosinophils , Fluorescent Antibody Technique , Gene Expression , Humans , Immunohistochemistry , Interleukin-13 , Interleukins , Mice , Models, Animal , Mucous Membrane , Nasal Polyps , Nose , Osteitis , Osteoblasts , Osteoclasts , Osteogenesis , Osteonectin , Ovalbumin , Polymerase Chain Reaction , Sinusitis , Transcription Factors , Transcriptome
18.
Article in Chinese | WPRIM | ID: wpr-880772

ABSTRACT

OBJECTIVE@#To investigate the effect of zoledronate (ZOL) on osteoclast differentiation and bone resorption under high glucose, and the regulation mechanism of p38 mitogen activated kinase (p38 MAPK) signaling pathway in this process.@*METHODS@#RAW264.7 cells were divided into four groups: low group, high group, low+ZOL group and high+ZOL group after induced into osteoclasts. Cell proliferation activity was determined by MTT assay. The migration of RAW264.7 cells were examined Optical microscopy. Immunofluorescence microscopy was used to observe the cytoskeleton and sealing zones of osteoclasts. After adding group 5: high + ZOL + SB203580 group, trap staining was used to identify the number of positive osteoclasts in each group. The number and area of resorption lacunae were observed by SEM. The mRNA and protein expression of osteoclast related factors were detected by real-time PCR and Western blotting.@*RESULTS@#The cells in the 5 groups showed similar proliferative activity. High glucose promoted the migration of RAW264.7 cells (@*CONCLUSIONS@#High glucose inhibits osteoclast differentiation and bone resorption. ZOL inhibits osteoclast differentiation and bone resorption in high-glucose conditions by regulating p38 MAPK pathway, which can be a new pathway for ZOL to regulate diabetic osteoporosis.


Subject(s)
Animals , Bone Resorption , Cell Differentiation , Glucose , MAP Kinase Signaling System , Mice , NFATC Transcription Factors , Osteoclasts , RANK Ligand , Zoledronic Acid/pharmacology , p38 Mitogen-Activated Protein Kinases
19.
Actual. osteol ; 16(3): 188-210, 2020. ilus, tab
Article in Spanish | LILACS | ID: biblio-1253839

ABSTRACT

Los micro-ARNs (miARNs) son pequeñas moléculas de ARN no codificante (de aproximadamente 15-25 nucleótidos), que regulan la expresión de genes involucrados en numerosas funciones biológicas, a través de la inhibición o degradación de un ARN mensajero diana. La homeostasis ósea se mantiene por el balance entre la formación osteoblástica y la resorción osteoclástica. La sobreexpresión o inhibición de miARNs específicos afecta la proliferación, diferenciación y actividad de osteoblastos, osteocitos y osteoclastos. Estas acciones son llevadas a cabo modulando la expresión de distintos factores transcripcionales y moléculas de señalización de las vías esenciales para la osteoblastogénesis u osteoclastogénesis. Estos efectos modifican el balance entre la formación y la resorción, determinando cambios en la homeostasis ósea. Esta revisión enumera una serie de miARNs que participan en la homeostasis ósea. Profundizando en el conocimiento de los mecanismos por medio de los cuales los miARNs actúan sobre el hueso, podrían revelarse nuevos usos potenciales futuros, entre los que se encuentran su utilidad como nuevos biomarcadores óseos o como agentes terapéuticos para el tratamiento de trastornos metabólicos óseos, pérdida de masa ósea o enfermedades óseas. (AU)


MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules (of approximately 15­25 nucleotides), which regulate the expression of genes controlling numerous biological functions, through the inhibition or degradation of the target messenger RNA. Bone homeostasis is maintained by a balance between osteoblastic bone formation and osteoclastic bone resorption. The overexpression or inhibition of specific miRNAs affects cell proliferation, differentiation and activity of osteoblast, osteocytes and osteoclast. This action is done by modulating the expression of different transcription factors and signaling molecules of the most relevant pathways of osteoblastogenesis or osteoclastogenesis. This effect is able to modify the balance between bone formation and resorption, determining changes in bone homeostasis. The present review is an overview of a series of miRNAs involved in bone homeostasis. An in depth knowledge of the mechanisms by which miRNAs act on bone may reveal potential uses in the future as new bone biomarkers or therapeutic agents for treating metabolic bone disorders, bone loss and bone diseases. (AU)


Subject(s)
Humans , Bone Remodeling , MicroRNAs/therapeutic use , Osteoblasts , Osteoclasts , Osteocytes , Skeleton/metabolism , Bone Diseases/therapy , Bone Resorption/therapy , Biomarkers , MicroRNAs/physiology , Fractures, Bone/prevention & control
20.
Braz. oral res. (Online) ; 34: e012, 2020. graf
Article in English | LILACS | ID: biblio-1089395

ABSTRACT

Abstract Lipoproteins are important bacterial immunostimulating molecules capable of inducing receptor activator of nuclear factor-κB (RANKL) and osteoclast formation in vitro and in vivo . Although these molecules are present in periodontopathogenic bacteria, their role in periodontitis is not known. In this study, we used Pam2CSK4 (PAM2), a synthetic molecule that mimics bacterial lipoprotein, to investigate the effects of lipoproteins on periodontitis in mice. C57BL/6 male mice were randomly divided into three experimental groups: 1) Negative control group: animals received vehicle injection; 2) Positive control group: animals received injection of Escherichia coli lipopolysaccharide (LPS); 3) PAM2 group: animals received PAM2 injection. All the injections were performed bilaterally every other day into the palatal mucosa between first and second molars. After twenty-four days, the animals were euthanized to assess alveolar bone volume (micro-CT), cellular and extracellular composition in the gingiva (stereometric analysis), and osteoclast numbers (TRAP staining). Treatment with either PAM2 or LPS induced gingival inflammation, as demonstrated by increased infiltration of inflammatory cells and enhanced angiogenesis, associated with a smaller number of fibroblasts and decreased extracellular matrix. Importantly, treatment not only with LPS but also with PAM2 resulted in a larger number of TRAP+ multinucleated osteoclasts and significant loss of alveolar bone. Collectively, our data demonstrate that PAM2 can induce gingival inflammation and bone loss in mice, broadening the avenues of investigation into the role of lipoproteins in the pathogenesis of periodontal disease.


Subject(s)
Animals , Male , Periodontitis/etiology , Periodontitis/pathology , Toll-Like Receptor 2/antagonists & inhibitors , Lipopeptides/pharmacology , Osteoclasts/drug effects , Osteoclasts/physiology , Periodontitis/microbiology , Time Factors , Random Allocation , Alveolar Bone Loss/etiology , Alveolar Bone Loss/pathology , Disease Models, Animal , X-Ray Microtomography , Alveolar Process/drug effects , Alveolar Process/pathology , Tartrate-Resistant Acid Phosphatase , Gingiva/drug effects , Gingiva/pathology , Gingivitis/etiology , Gingivitis/pathology , Mice, Inbred C57BL
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