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1.
Bone ; 160: 116424, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35460961

RESUMO

Bone's ability to adapt is governed by the network of embedded osteocytes, which inhabit individual pores called lacunae. The morphology of these lacunae and their resident osteocytes are known to change with age and diseases such as postmenopausal osteoporosis. However, it is unclear whether alterations in lacunar morphology are present in younger populations with osteoporosis. To investigate this, we implemented a previously validated methodology to image and quantify the three-dimensional morphometries of lacunae on a large scale with ultra-high-resolution micro-computed tomography (microCT) in transiliac bone biopsies from three groups of premenopausal women: control n = 39; idiopathic osteoporosis (IOP) n = 45; idiopathic low BMD (ILBMD) n = 19. Lacunar morphometric parameters were measured in both trabecular and cortical bone such as lacunar density (Lc.N/BV), lacunar volume (Lc.V), and lacunar sphericity (Lc.Sr). These were then compared against each other and also with previously measured tissue morphometries such as bone volume density (BV/TV), trabecular separation (Tb.Sp), trabecular number (Tb.N), and others. We detected no differences in lacunar morphology between the IOP, ILBMD and healthy premenopausal women. In contrast, we did find significant differences between lacunar morphologies including Lc.N/BV, Lc. V, and Lc. Sr in cortical and trabecular regions within all three groups (p < 0.001), which was consistent with our previous findings on a subgroup of the healthy group. Furthermore, we discovered strong correlations between Lc. Sr from trabecular regions with the measured BV/TV (R = -0.90, p < 0.05). The findings and comprehensive lacunar dataset we present here will be a crucial foundation for future investigations of the relationship between osteocyte lacunar morphology and disease.


Assuntos
Osteócitos , Osteoporose , Densidade Óssea , Osso e Ossos , Feminino , Humanos , Osteócitos/patologia , Osteoporose/diagnóstico por imagem , Osteoporose/patologia , Microtomografia por Raio-X
2.
Bioengineered ; 13(4): 10866-10874, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35473505

RESUMO

Osteoporosis is a systemic disorder of bone metabolism. This study aimed to investigate the impacts and possible mechanisms of Arctiin, a lignin isolated from Arctium lappa on MC3T3-E1 osteoblast differentiation. In this study, after treatment with different concentrations of Arctiin, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to estimate the expression of osteogenesis markers. Then, the activity of alkaline phosphatase (ALP) was detected by an ALP assay kit and calcium nodules staining was evaluated by alizarin red staining (ARS). Additionally, the regulatory effects of Arctiin on cyclin D1 (Ccnd1) was assessed by measurement of protein expression. Subsequently, the functions of Ccnd1 silencing on the osteogenic differentiation was examined in Arctiin-treated MC3T3-E1 cells. Results indicated that Arctiin dose-dependently upregulated the expression of runt-related transcription factor 2 (RUNX2), collagen type 1 (COL1A1), osteocalcin (OCN) and osteopontin (OPN). Elevated ALP activity and calcification degree was prominently observed in the Arctiin-treated groups. Moreover, Ccnd1 expression was notably enhanced after Arctiin intervention. Importantly, Ccnd1-knockdown abrogated the impacts of Arctiin on osteogenic differentiation of MC3T3-E1. To conclude, findings in this study suggested that Arctiin could regulate MC3T3-E1 osteoblast differentiation via up-regulating Ccnd1, supporting that Arctiin might be a therapeutic target for osteoporosis.


Assuntos
Ciclina D1 , Furanos , Glucosídeos , Osteogênese , Osteoporose , Animais , Ciclina D1/genética , Ciclina D1/metabolismo , Furanos/farmacologia , Glucosídeos/farmacologia , Camundongos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteogênese/genética , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia
3.
Front Endocrinol (Lausanne) ; 13: 817418, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265038

RESUMO

Purpose: The etiology of age-related bone loss is less clear in men. This study is aimed to observe the variations of endogenous sex hormone concentrations with increasing of age in men, and investigate their relations to bone mass, marrow adiposity, and muscle adiposity. Methods: A total of 199 community-dwelling Chinese men (aged 41 to 82 years) were included and measured of serum total estradiol, total testosterone, and follicle-stimulating hormone (FSH) concentrations by enzyme-linked immunosorbent assay (ELISA). Vertebral trabecular volumetric bone mineral density (vBMD) was measured by quantitative computed tomography for all participants, and vertebral marrow fat content and erector muscle fat content were quantified by Chemistry-shift-encoding magnetic resonance imaging in 62 participants. Results: In this population, FSH concentration increased (p < 0.001) gradually with aging. Lower vBMD was independently associated with higher FSH concentration (ß = -0.216, p < 0.001), but not with total estradiol or total testosterone. For each standard deviation increase in FSH there was a 50% higher risk of an individual having osteopenia or osteoporosis (vBMD < 120 mg/cm3). Marrow fat content and erector muscle fat content were greater in osteopenic and osteoporotic men, but there were no associations with sex hormones concentrations. Conclusion: In summary, FSH but not total estradiol or total testosterone is related to vertebral trabecular vBMD in middle-aged and older Chinese men. Neither marrow adiposity nor muscle adiposity is associated with sex hormones.


Assuntos
Densidade Óssea , Osteoporose , Adiposidade/fisiologia , Idoso , Densidade Óssea/fisiologia , Medula Óssea/patologia , Estradiol , Hormônio Foliculoestimulante , Hormônios Esteroides Gonadais , Humanos , Masculino , Pessoa de Meia-Idade , Músculos , Obesidade , Osteoporose/etiologia , Osteoporose/patologia , Testosterona
4.
Front Endocrinol (Lausanne) ; 13: 826660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273570

RESUMO

Previous studies have revealed that melatonin could play a role in anti-osteoporosis and promoting osteogenesis. However, the effects of melatonin treatment on osteoporotic bone defect and the mechanism underlying the effects of melatonin on angiogenesis are still unclear. Our study was aimed to investigate the potential effects of melatonin on angiogenesis and osteoporotic bone defect. Bone marrow mesenchymal stem cells (BMSCs) were isolated from the femur and tibia of rats. The BMSC osteogenic ability was assessed using alkaline phosphatase (ALP) staining, alizarin red S staining, qRT-PCR, western blot, and immunofluorescence. BMSC-mediated angiogenic potentials were determined using qRT-PCR, western blot, enzyme-linked immunosorbent assay, immunofluorescence, scratch wound assay, transwell migration assay, and tube formation assay. Ovariectomized (OVX) rats with tibia defect were used to establish an osteoporotic bone defect model and then treated with melatonin. The effects of melatonin treatment on osteoporotic bone defect in OVX rats were analyzed using micro-CT, histology, sequential fluorescent labeling, and biomechanical test. Our study showed that melatonin promoted both osteogenesis and angiogenesis in vitro. BMSCs treated with melatonin indicated higher expression levels of osteogenesis-related markers [ALP, osteocalcin (OCN), runt-related transcription factor 2, and osterix] and angiogenesis-related markers [vascular endothelial growth factor (VEGF), angiopoietin-2, and angiopoietin-4] compared to the untreated group. Significantly, melatonin was not able to facilitate human umbilical vein endothelial cell angiogenesis directly, but it possessed the ability to promote BMSC-mediated angiogenesis by upregulating the VEGF levels. In addition, we further found that melatonin treatment increased bone mineralization and formation around the tibia defect in OVX rats compared with the control group. Immunohistochemical staining indicated higher expression levels of osteogenesis-related marker (OCN) and angiogenesis-related markers (VEGF and CD31) in the melatonin-treated OVX rats. Then, it showed that melatonin treatment also increased the bone strength of tibia defect in OVX rats, with increased ultimate load and stiffness, as performed by three-point bending test. In conclusion, our study demonstrated that melatonin could promote BMSC-mediated angiogenesis and promote osteogenesis-angiogenesis coupling. We further found that melatonin could accelerate osteoporotic bone repair by promoting osteogenesis and angiogenesis in OVX rats. These findings may provide evidence for the potential application of melatonin in osteoporotic bone defect.


Assuntos
Melatonina , Osteoporose , Animais , Diferenciação Celular , Melatonina/farmacologia , Melatonina/uso terapêutico , Osteogênese , Osteoporose/patologia , Ratos , Fator A de Crescimento do Endotélio Vascular
5.
Comput Math Methods Med ; 2022: 9619867, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309846

RESUMO

Objective: To evaluate the influence of sinusoidal vibration (50-Hertz) stimulation on the uterus of osteoporotic rats. Methods: We constructed an osteoporosis rat model by ovariectomy (OVX). 36 3-month-old Sprague Dawley rats were randomly divided into the control group, vibrating group, sham operation group, sham operation vibrating group, OVX group, and OVX vibrating group (n = 6 per group). Rats started to vibrate one week after the operation: one 10 minutes 50-Hertz sinusoidal vibration per day, except for Saturday and Sunday. In the second, 8, and 12 week after vibration stimulation, rats were sacrificed in batches. And then, the uteruses were taken out to measure the wet weight and calculate uterus relative wet weight. Results: Compared with the control group, OVA induced a significant increase in wet weight and relative wet weight in rat uterus. The vibration was to the uterus wet weight and the uterus relative wet weight in ovariectomized rats and at the same time had no significant effect, but the 12-week prolonged vibration can significantly reduce the uterus wet weight and the uterus relative wet weight in ovariectomized rats than 2 weeks. Conclusions: The uterus wet weight and the uterus relative wet weight were increased in the OVA-induced osteoporosis rats. The 50-Hertz sinusoidal vibration had no significant effect on the uterus wet weight and the uterus relative wet weight in the ovariectomized rats at the same time, but 12 weeks of vibration can significantly reduce the uterine wet weight and uterine relative wet weight of ovariectomized rats. And the uterus relative wet weight can be used as a new indicator of stimulating the uterus.


Assuntos
Osteoporose/etiologia , Osteoporose/terapia , Ovariectomia/efeitos adversos , Útero/patologia , Vibração/uso terapêutico , Animais , Biologia Computacional , Modelos Animais de Doenças , Feminino , Tamanho do Órgão , Osteoporose/patologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
6.
Genes (Basel) ; 13(2)2022 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-35205249

RESUMO

BACKGROUND: Osteoporosis is a skeletal disease with a strong genetic background. The study aimed to identify the genetic determinants of early-onset familial osteoporosis and low bone mineral density (BMD) in a two-generation Maltese family. METHODS: Fifteen relatives aged between 28-74 years were recruited. Whole genome sequencing was conducted on 12 relatives and shortlisted variants were genotyped in the Malta Osteoporotic Fracture Study (MOFS) for replication. RESULTS: Sequential variant filtering following a dominant inheritance pattern identified rare missense variants within SELP, TGF-ß2 and ADAMTS20, all of which were predicted to be likely pathogenic and participate in osteoimmunology. TGF-ß2 c.1136C>T was identified in five individuals from the MOFS in heterozygosity, four of whom had osteopenia/osteoporosis at the lumbar spine and hip, and/or had sustained a low-trauma fracture. Heterozygosity for the ADAMTS20 c.4090A>T was accompanied by lower total hip BMD (p = 0.018) and lower total serum calcium levels in MOFS (p < 0.01), recapitulating the findings from the family. Women carrying at least one copy of the alternative allele (TC/CC) for SELP c.2177T>C exhibited a tendency for lower lumbar spine BMD and/or wrist fracture history relative to women with TT genotype. CONCLUSIONS: Our findings suggest that the identified variants, alone or in combination, could be causal factors of familial osteoporosis and low BMD, requiring replication in larger collections.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Fraturas por Osteoporose , Adulto , Idoso , Densidade Óssea/genética , Feminino , Humanos , Malta , Pessoa de Meia-Idade , Osteoporose/genética , Osteoporose/patologia , Fator de Crescimento Transformador beta2/genética , Sequenciamento Completo do Genoma
7.
J Cell Mol Med ; 26(8): 2163-2176, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35181992

RESUMO

Inflammation is a major risk factor for osteoporosis, and reducing inflammatory levels is important for the prevention of osteoporosis. Although nuclear receptor 77 (Nur77) protects against inflammation in a variety of diseases, its role in osteoporosis is unknown. Therefore, the main purpose of this study was to investigate the osteoprotective and anti-inflammatory effects of Nur77. The microCT and haematoxylin and eosin staining results indicated that knockout of Nur77 accelerated femoral bone loss in mice. The enzyme-linked immunosorbent assay (ELISA) results showed that knockout of Nur77 increased the serum levels of hsCRP and IL-6. The expression levels of NF-κB, IL-6, TNF-α and osteoclastogenesis factors (TRAP, NFATC1, Car2, Ctsk) in the femurs of Nur77 knockout mice were increased significantly. Furthermore, in vitro, shNur77 promoted the differentiation of RAW264.7 cells into osteoclasts by activating NF-κB, which was confirmed by PDTC treatment. Mechanistically, Nur77 inhibited osteoclast differentiation by inducing IκB-α and suppressing IKK-ß. In RAW264.7 cells, overexpression of Nur77 alleviated inflammation induced by siIκB-α, while siIKK-ß alleviated inflammation induced by shNur77. Consistent with the in vivo studies, we found that compared with control group, older adults with high serum hsCRP levels were more likely to suffer from osteoporosis (OR = 1.76, p < 0.001). Our data suggest that Nur77 suppresses osteoclast differentiation by inhibiting the NF-κB signalling pathway, strongly supporting the notion that Nur77 has the potential to prevent and treat osteoporosis.


Assuntos
NF-kappa B , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Osteoporose , Animais , Proteína C-Reativa/metabolismo , Diferenciação Celular , Inflamação/metabolismo , Interleucina-6/metabolismo , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Osteoclastos/metabolismo , Osteogênese , Osteoporose/genética , Osteoporose/patologia , Osteoporose/prevenção & controle , Ligante RANK/metabolismo , Células RAW 264.7 , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais
8.
Ann Clin Lab Sci ; 52(1): 48-59, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35181618

RESUMO

OBJECTIVE: Osteoporosis is likely becoming a new disease challenge with increasing aging population. Circ_0006873 dysregulation may serve as an event linked to osteoporosis. Thus, this study sought to evaluate the function and mechanism of circ_0006873 on osteoporosis. METHODS: Clinical serum samples collected from 30 osteoporosis patients were utilized to obtain circ_0006873 and miR-142-5p expression data. The link between circ_0006873, miR-142-5p, and phosphatase and tensin homolog (PTEN) was demonstrated via online tools (starBase, circinteractome), RNA Immunoprecipitation (RIP) and dual-Luciferase reporter assays. After knockdown or overexpression, cell counting kit-8 (CCK-8) assay measured cell viability. Alizarin red S (ARS) staining as well Alkaline phosphatase (ALP) staining detected osteoblastic differentiation levels. Quantitative real-time PCR (qRT-PCR) and western blot analyzed expression of RNAs and proteins after transfection or during osteoblastic differentiation. RESULTS: circ_0006873 was upregulated in osteoporosis patients and decreased during osteoblastic differentiation. Following experiments revealed that cell viability, proliferation-related factors, osteogenic marker genes (ALP, Runx2, Bglap) and osteoblastic differentiation degree were promoted after circ_0006873 knockdown but inhibited after overexpression. Circ_0006873 sponged miR-142-5p, which was downregulated in osteoporosis patients and became higher during osteoblastic differentiation. Rescue assay indicated miR-142-5p mimic could reverse the effects of circ_0006873 overexpression on cell viability and osteogenic markers, and also could activate Akt pathway. Furthermore, circ_0006873 can negatively target miR-142-5p via regulating PTEN to inhibit osteoblastic differentiation. CONCLUSION: Circ_0006873 sponges miR-142-5p thereby enhances PTEN expression to suppress osteoblastic differentiation via regulation of Akt signaling pathway, thus, may provide a treatment approach for osteoporosis.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Osteoblastos , Osteoporose , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas c-akt , RNA Circular , Idoso , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoporose/sangue , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Transdução de Sinais
9.
Int J Mol Sci ; 23(4)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35216140

RESUMO

Osteoporosis (OP) is a systemic bone disease characterized by decreased bone strength, microarchitectural changes in bone tissues, and increased risk of fracture. Its occurrence is closely related to various factors such as aging, genetic factors, living habits, and nutritional deficiencies as well as the disturbance of bone homeostasis. The dysregulation of bone metabolism is regarded as one of the key influencing factors causing OP. Cholesterol oxidation products (COPs) are important compounds in the maintenance of bone metabolic homeostasis by participating in several important biological processes such as the differentiation of mesenchymal stem cells, bone formation in osteoblasts, and bone resorption in osteoclasts. The effects of specific COPs on mesenchymal stem cells are mainly manifested by promoting osteoblast genesis and inhibiting adipocyte genesis. This review aims to elucidate the biological roles of COPs in OP development, starting from the molecular mechanisms of OP, pointing out opportunities and challenges in current research, and providing new ideas and perspectives for further studies of OP pathogenesis.


Assuntos
Colesterol/metabolismo , Osteoporose/metabolismo , Osteoporose/patologia , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Humanos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteogênese/fisiologia , Oxirredução
10.
Int J Mol Sci ; 23(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35054977

RESUMO

Vitamin D plays an essential role in prevention and treatment of osteoporosis. Thyroid hormones, in addition to vitamin D, significantly contribute to regulation of bone remodeling cycle and health. There is currently no data about a possible connection between vitamin D treatment and the thyroid in the context of osteoporosis. Middle-aged Wistar rats were divided into: sham operated (SO), orchidectomized (Orx), and cholecalciferol-treated orchidectomized (Orx + Vit. D3; 5 µg/kg b.m./day during three weeks) groups (n = 6/group). Concentration of 25(OH)D in serum of the Orx + Vit. D3 group increased 4 and 3.2 times (p < 0.0001) respectively, compared to Orx and SO group. T4, TSH, and calcitonin in serum remained unaltered. Vit. D3 treatment induced changes in thyroid functional morphology that indicate increased utilization of stored colloid and release of thyroid hormones in comparison with hormone synthesis, to maintain hormonal balance. Increased expression of nuclear VDR (p < 0.05) points to direct, TSH independent action of Vit. D on thyrocytes. Strong CYP24A1 immunostaining in C cells suggests its prominent expression in response to Vit. D in this cell subpopulation in orchidectomized rat model of osteoporosis. The indirect effect of Vit. D on bone, through fine regulation of thyroid function, is small.


Assuntos
Colecalciferol/farmacologia , Osteoporose/etiologia , Osteoporose/metabolismo , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Animais , Biomarcadores , Peso Corporal , Modelos Animais de Doenças , Suscetibilidade a Doenças , Imunofluorescência , Hormônios/metabolismo , Imuno-Histoquímica , Masculino , Orquiectomia , Tamanho do Órgão , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Ratos , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Células Epiteliais da Tireoide/efeitos dos fármacos , Células Epiteliais da Tireoide/metabolismo , Glândula Tireoide/patologia , Glândula Tireoide/ultraestrutura , Vitamina D3 24-Hidroxilase/metabolismo
11.
Biomed Pharmacother ; 147: 112640, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35033946

RESUMO

Pyrrosia lingua (Thunb.) Farw is a common plant that has been widely used as a traditional herbal medicine in China and Korea to treat patients suffering from pain, vaginal bleeding and urolithiasis. However, the pharmacological effects of P. lingua on bone remain unknown. We investigated the anti-osteoporotic effects of an ethanolic extract of P. lingua (EEPL). We found that EEPL suppressed osteoclast differentiation by directly acting on osteoclast precursor cells. EEPL suppressed the expression of receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor of activated T cells 1, a major transcription factor for osteoclastogenesis, by inhibiting RANKL-induced expression of aryl hydrocarbon receptor/c-Fos, and activation of nuclear factor-κB and mitogen-activated protein kinases. Moreover, administration of EEPL inhibited trabecular bone loss and weight gain in ovariectomized mice. Furthermore, we identified phytochemicals in EEPL that are known to exert anti-osteoclastogenic or anti-osteoporotic effects using ultra-high-performance liquid chromatography-tandem mass-spectrometry analysis. Overall, the results of this study suggest that EEPL is effective therapeutic candidate that can be used to prevent or treat postmenopausal osteoporosis.


Assuntos
Osteoclastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polypodiaceae , Ligante RANK/efeitos dos fármacos , Animais , Osso Esponjoso/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Osteoporose/patologia , Ovariectomia , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
12.
Biomed Pharmacother ; 147: 112631, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35033947

RESUMO

Norzoanthamine (NZ), an alkaloid that has been isolated from the marine cnidiaria Zoanthus sp., has been shown an interesting anti-osteoporotic activity. Although its mechanism of action is not yet clear, it seems that it is different from those of currently used drugs making it particularly interesting. Previous studies have been carried out mostly in vitro. Herein, we present an in vivo study that allows to check the real potential of NZ as a protector substance by direct application into ovariectomized rat bone using a sustained delivery system. Histological and histomorphometric results in ovariectomized rats showed higher bone quality as a result of greater number of trabeculae and osteogenic activity in the group implanted with NZ, compared to controls. In contrast with the untreated controls, NZ-treated groups showed a balanced osteoblast/osteoclast number ratio, similar to that found in the normal bone. These results suggest that NZ could be useful as adjunct to other osteoporosis treatments, but probably its main therapeutic role would be as preventive therapy against bone deterioration.


Assuntos
Alcaloides/farmacologia , Azepinas/farmacologia , Produtos Biológicos/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Osteoporose/patologia , Quinolinas/farmacologia , Animais , Densidade Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Feminino , Microesferas , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Ovariectomia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Ratos Sprague-Dawley
13.
Int J Mol Sci ; 23(2)2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35054874

RESUMO

Irisin is a peptide secreted by skeletal muscle following exercise that plays an important role in bone metabolism. Numerous experiments in vitro and in mouse models have shown that the administration of recombinant irisin promotes osteogenesis, protects osteocytes from dexamethasone-induced apoptosis, prevents disuse-induced loss of bone and muscle mass, and accelerates fracture healing. Although some aspects still need to be elucidated, such as the dose- and frequency-dependent effects of irisin in cell cultures and mouse models, ample clinical evidence is emerging to support its physiological relevance on bone in humans. A reduction in serum irisin levels, associated with an increased risk of osteoporosis and bone fractures, was observed in postmenopausal women and in both men and women during aging, Recently, cohort studies of subjects with secondary osteoporosis showed that these patients have lower circulating levels of irisin, suggesting that this myokine could be a novel marker to monitor bone quality in this disease. Although there are still few studies, this review discusses the emerging data that are highlighting the involvement of irisin in some diseases that cause secondary osteoporosis.


Assuntos
Fibronectinas/metabolismo , Osteoporose/patologia , Humanos , Modelos Biológicos , Proteínas Recombinantes/farmacologia
14.
Mol Cell Endocrinol ; 540: 111520, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34838695

RESUMO

Osteoporosis (OP) is characterized by decreased bone mineral density and impaired bone strength. Carfilzomib (CFZ) is a new-generation proteasome inhibitor and has been found to affect bone metabolism. However, the effect and mechanism of CFZ on OP has not been investigated systematically. In this study, we found that protein levels of proteasome activator subunit 1/2 (PSME1/2) increased in OP, and accumulated mostly in osteoblasts and osteoclasts. Treatment with PSME1/2 recombinant protein inhibited osteogenesis and promoted osteoclast formation in vitro. Also, PSME1/2 inhibited the expression of ß-catenin protein, resulting in limitation of Wnt/ß-catenin signaling. CFZ inhibited PSME1 and PSME2 proteasome activities and increased ß-catenin protein level, resulting in the translocation of ß-catenin to the nucleus and activation of canonical Wnt/ß-catenin signaling, further promoting osteogenesis and inhibiting osteoclastic differentiation. In vivo, we conducted ovariectomy (OVX) to create a model of OVX-induced postmenopausal OP in mice. When analyzed by micro-CT scanning, enhancement of bone mineral density, bone volume, trabecular number, and thickness was seen in the CFZ-treated mice. Also, we noticed increased osteogenesis and decreased osteoclastogenesis, diminished expression of PSME1 and PSME2 and activated Wnt/ß-catenin signaling in bone sections from OP mice treated with CFZ. Overall, our data indicated that PSME1/2 may serve as new targets for the treatment of OP, and targeting PSME1/2 with CFZ provides a candidate therapeutic molecule for postmenopausal OP.


Assuntos
Oligopeptídeos/uso terapêutico , Osteoporose/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma/genética , Animais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/genética , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/genética , Células Cultivadas , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteoporose/patologia , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Células RAW 264.7 , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo
15.
Osteoporos Int ; 33(4): 861-869, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34773484

RESUMO

Magnetic resonance imaging (MRI) is a routine assessment before spine surgery. We found that the opportunistic use of MRI with the vertebral bone quality (VBQ) score has good diagnostic ability, with a threshold value of VBQ > 3.0, in recognizing patients who may need further osteoporosis evaluation. INTRODUCTION: The purpose of this study was to determine whether the opportunistic use of magnetic resonance imaging (MRI) is useful for identifying spine surgical patients who need further osteoporosis evaluation. METHODS: This retrospective study evaluated 83 thoracolumbar spine surgery patients age ≥ 50 who received T1-weighted MRI. Opportunistic MRI was evaluated with the vertebral bone quality (VBQ) score, VBQ (fat) score, and signal-to-noise ratio (SNR). Each uses the median L1-L4 vertebral body signal intensities (SI) divided by either the L3 cerebrospinal fluid (CSF) SI, average SI of the L1 and S1 dorsal fat, or standard deviation (SD) of the background SI dorsal to the skin. Single-level VBQ was calculated as the ratio of the L1 vertebral body and L1 CSF SIs. Receiver-operator curve analysis was performed to determine diagnostic ability. RESULTS: The mean age was 70.10, 80% were female, and 96% were Caucasian. The mean ± SD VBQ, single-level VBQ, VBQ (fat), and SNR were 3.39 ± 0.68, 3.56 ± 0.81, 3.95 ± 1.89, and 113.18 ± 77.26, respectively. Using area under the curve, the diagnostic ability of VBQ, single-level VBQ, VBQ (fat), and SNR for clinical osteoporosis were 0.806, 0.779, 0.608, and 0.586, respectively. Diagnostic threshold values identified with optimal sensitivity and specificity were VBQ of 2.95 and single-level VBQ of 3.06. CONCLUSION: Opportunistic use of MRI is a simple, effective tool that may help recognize patients who are at risk for complications related to bone disease. A VBQ > 3.0 can identify patients who need additional diagnostic evaluation.


Assuntos
Vértebras Lombares , Osteoporose , Idoso , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Região Lombossacral , Imageamento por Ressonância Magnética , Osteoporose/diagnóstico por imagem , Osteoporose/patologia , Estudos Retrospectivos
16.
Chem Biol Drug Des ; 99(1): 46-55, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34145772

RESUMO

Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and bone quality and increased bone porosity, which increase the risk of bone fracture. Inflammation, one of the important mechanisms related to aging, is associated with osteoporosis. Treatment with anti-inflammatory agents is effective for alleviating senile osteoporosis. Alginate oligosaccharide (AOS) can prevent and treat diseases related to inflammation, oxidative stress, and immunity. This study evaluates the effect of AOS on osteoporosis and investigates the underlying mechanism. Osteoporosis model was induced by D-galactose (D-gal) (200 mg kg-1  day-1 ) for eight weeks. Three groups were administered via AOS (50, 100, and 150 mg kg-1  day-1 ) for four weeks, while a control group received sterile water (5 ml kg-1  day-1 ) for 8 weeks. The results showed that AOS improved bone density and bone microstructure in D-gal-induced osteoporosis mice. AOS inhibited osteoclast proliferation, probably through the suppression of receptor activator of nuclear factor-kappa B ligand (RANKL)-associated nuclear factor kappa B (NF-κB) and c-Fos signaling pathway. AOS also increased osteoprotegerin (OPG) expression and competitively inhibited the binding between RANK and RANKL in senile osteoporosis. Further, AOS decreased the secretion of serum osteocalcin and reduced bone conversion. Together, these results demonstrate the anti-osteoporosis activity of AOS in mice with osteoporosis.


Assuntos
Alginatos/química , Galactose/farmacologia , Oligossacarídeos/química , Oligossacarídeos/uso terapêutico , Osteoporose/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Densidade Óssea/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Oligossacarídeos/farmacologia , Osteoporose/patologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos
17.
Life Sci ; 290: 119480, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33862113

RESUMO

AIMS: Bone defect repair in osteoporosis remains a tremendous challenge for clinicians due to increased bone metabolism resulted from estrogen deficiency. This study aims to investigate the effect of bone marrow mesenchymal stem cells (BMSCs) combined with fibrin glue (FG) in the extraction socket healing process of osteoporosis rats, as well as estimate the role of estrogen receptors (ERs) played in BMSCs differentiation in vitro and in the alveolar bone reconstruction process in vivo. MAIN METHODS: Forty rats were randomly divided into four groups, under general anesthesia, three groups underwent bilateral ovariectomy(OVX) and one group with the sham operation. Three months later, the osteogenic ability of BMSCs, isolated from healthy and osteoporosis rats, respectively, was tested. The ERα and ERß mRNA expression in BMSCs was also evaluated by RT-PCR analysis. In vivo experiment, Micro-CT detection, histological and immunofluorescent analysis, tissue PCR was conducted up to 2, 4 and 6 weeks after transplantation of BMSCs/FG to assess the newly formed bone in the extraction socket. KEY FINDINGS: The BMSCs from osteoporosis rats displayed weaker osteogenic potential and lower ERs expression compared with the BMSCs from healthy rats. Newly formed bone tissue filled the socket defect in BMSCs/FG treated VOX rats after six weeks, which was comparable to the sham group, while reduced ERs expression was found in the regenerated bone of the OVX group. SIGNIFICANCE: The BMSCs seeded within FG might provide an alternative therapeutic method for repairing the extraction socket defect in osteoporosis condition.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Adesivo Tecidual de Fibrina/farmacologia , Transplante de Células-Tronco Mesenquimais/métodos , Osteoporose/terapia , Alvéolo Dental/efeitos dos fármacos , Animais , Densidade Óssea , Regeneração Óssea/fisiologia , Diferenciação Celular , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Maxila/efeitos dos fármacos , Maxila/fisiopatologia , Células-Tronco Mesenquimais/citologia , Osteoporose/patologia , Osteoporose/fisiopatologia , Ovariectomia , Ratos Sprague-Dawley , Receptores de Estrogênio/genética , Extração Dentária/efeitos adversos
18.
Biomed Pharmacother ; 146: 112547, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34929579

RESUMO

Prolonged exposure to polycyclic aromatic hydrocarbons (PAHs) may result in autoimmune diseases, such as rheumatoid arthritis (RA) and osteoporosis (OP), which are based on an imbalance in bone homeostasis. These diseases are characterized by bone erosion and even a disruption in homeostasis, including in osteoblasts and osteoclasts. Current evidence indicates that multiple factors affect the progression of bone homeostasis, such as genetic susceptibility and epigenetic modifications. However, environmental factors, especially PAHs from various sources, have been shown to play an increasingly prominent role in the progression of bone homeostasis. Hence, it is essential to investigate the effects and pathogenesis of PAHs in bone homeostasis. In this review, recent progress is summarized concerning the effects and mechanisms of PAHs and their ligands and receptors in bone homeostasis. Moreover, strategies based on the effects and mechanisms of PAHs in the regulation of the bone balance and alleviation of bone destruction are also reviewed. We further discuss the future challenges and perspectives regarding the roles of PAHs in autoimmune diseases based on bone homeostasis.


Assuntos
Osso e Ossos/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Homeostase/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Exposição Ambiental/análise , Poluentes Ambientais/análise , Humanos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Proteína Oncogênica v-akt/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoporose/patologia , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/análise , Transdução de Sinais/efeitos dos fármacos
19.
Biomed Pharmacother ; 146: 112583, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34954644

RESUMO

Andrographis paniculata (A. paniculata) is a traditional herbal medicine that has been widely used in Asian countries for hundreds of years. Andrographolide (AG) is a diterpene lactone extracted from A. paniculata. Owing to the in-depth study of pharmacological mechanisms, the therapeutic potential of AG, including its anti-inflammatory, anti-tumor, and immunoregulatory attributes, has attracted the attention of many researchers. Studies testing the therapeutic effects of AG have demonstrated desirable results in the treatment of a variety of clinical diseases. With high safety and various biological functions, AG might be a promising candidate for the treatment of musculoskeletal disorders. Here, we review all available literatures to summarize the pharmacological effects of AG and facilitate further researches on musculoskeletal diseases.


Assuntos
Diterpenos/farmacologia , Doenças Musculoesqueléticas/patologia , Animais , Artrite/patologia , Linhagem Celular , Diterpenos/efeitos adversos , Diterpenos/farmacocinética , Interações Medicamentosas , Humanos , Degeneração do Disco Intervertebral/patologia , Medicina Tradicional , Osteoporose/patologia
20.
Biochem Pharmacol ; 197: 114888, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34968494

RESUMO

Type 1 diabetes (T1D)-induced osteoporosis is characterized by decreased bone mineral density, bone quality, rate of bone healing, bone formation, and increased bone resorption. Patients with T1D have a 2-7-fold higher risk of osteoporotic fracture. The mechanisms leading to increased risk of osteoporotic fracture in T1D include insulin deficiency, hyperglycemia, insulin resistance, lower insulin-like growth factor-1, hyperglycemia-induced oxidative stress, and inflammation. In addition, a higher probability of falling, kidney dysfunction, weakened vision, and neuropathy indirectly increase the risk of osteoporotic fracture in T1D patients. Decreased nitric oxide (NO) bioavailability contributes to the pathophysiology of T1D-induced osteoporotic fracture. This review discusses the role of NO in osteoblast-mediated bone formation and osteoclast-mediated bone resorption in T1D. In addition, the mechanisms involved in reduced NO bioavailability and activity in type 1 diabetic bones as well as NO-based therapy for T1D-induced osteoporosis are summarized. Available data indicates that lower NO bioavailability in diabetic bones is due to disruption of phosphatidylinositol 3­kinase/protein kinase B/endothelial NO synthases and NO/cyclic guanosine monophosphate/protein kinase G signaling pathways. Thus, NO bioavailability may be boosted directly or indirectly by NO donors. As NO donors with NO-like effects in the bone, inorganic nitrate and nitrite can potentially be used as novel therapeutic agents for T1D-induced osteoporosis. Inorganic nitrites and nitrates can decrease the risk for osteoporotic fracture probably directly by decreasing osteoclast activity, decreasing fat accumulation in the marrow cavity, increasing osteoblast activity, and increasing bone perfusion or indirectly, by improving hyperglycemia, insulin resistance, and reducing body weight.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Óxido Nítrico/fisiologia , Osteoporose/metabolismo , Fraturas por Osteoporose/metabolismo , Animais , Densidade Óssea/fisiologia , Reabsorção Óssea/epidemiologia , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Humanos , Osteoporose/epidemiologia , Osteoporose/patologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/patologia
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