Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.034
Filtrar
1.
Metabolism ; 118: 154730, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33607194

RESUMO

BACKGROUND: Human differentiated embryonic chondrocyte expressed gene 1 (DEC1) has been implicated in enhancing osteogenesis, a desirable outcome to counteract against deregulated bone formation such as retarded bone development, osteopenia and osteoporosis. METHODS AND RESULTS: DEC1 knockout (KO) and the age-matched wild-type (WT) mice were tested for the impact of DEC1 deficiency on bone development and osteopenia as a function of age. DEC1 deficiency exhibited retarded bone development at the age of 4 weeks and osteopenic phenotype in both 4- and 24-week old mice. However, the osteopenia was more severe in the 24-week age groups. Mechanistically, DEC1 deficiency downregulated the expression of bone-enhancing genes such as Runx2 and ß-catenin accompanied by upregulating DKK1, an inhibitor of the Wnt/ß-catenin signaling pathway. Consistently, DEC1 deficiency favored the attenuation of the integrated PI3KCA/Akt/GSK3ß signaling, a pathway targeting ß-catenin for degradation. Likewise, the attenuation was greater in the 24-week age group. These changes, however, were reversed by in vivo treatment with lithium chloride, a stabilizer of ß-catenin, and confirmed by gain-of-function study with DEC1 transfection into DEC1 KO bone marrow mesenchymal stem cells and loss-of-function study with siDEC1 lentiviral infection into the corresponding WT cells. CONCLUSION: DEC1 is a positive regulator with a broad activity spectrum in both bone development and maintenance, and the osteopenic phenotype accelerated by DEC1 deficiency is achieved by enhanced DKK1 activity and attenuated PI3KCA/Akt/GSK3ß signaling.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Animais , Desenvolvimento Ósseo , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/patologia , Diferenciação Celular , Progressão da Doença , Humanos , Camundongos , Camundongos Knockout , Osteoblastos/citologia , beta Catenina/metabolismo
2.
Ann N Y Acad Sci ; 1487(1): 43-55, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33107070

RESUMO

Whether T cells promote bone loss following immobilization after spinal cord injury (SCI) remains undetermined. Therefore, wild-type (WT) and T cell-deficient (Tcrb-/- ) male mice underwent sham or contusion SCI to cause hindlimb paralysis. Femurs were isolated and distal and midshaft regions were evaluated by microcomputed tomography scanning. Bone marrow (BM) levels of bone turnover markers, as well as receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG), were measured by ELISA. At 2 weeks post-SCI, immobilization resulted in marked reduction in trabecular fractional bone volume (55%), thickness (40%), connectivity, and cortical thickness only in the Tcrb-/- animals (interaction with P < 0.05). BM analysis revealed lower bone formation (procollagen type 1 intact N-terminal propeptide), higher bone resorption (tartrate-resistant acid phosphatase-5b), and a higher RANKL/OPG ratio in the Tcrb-/- SCI animals. At 5 weeks post-SCI, while both WT and Tcrb-/- paralyzed animals showed deterioration of all indices of bone structure, they were more severe in Tcrb-/- animals. In summary, unlike other skeletal disorders, loss of αß T cells compromises, rather than preserves, skeletal integrity under conditions of immobilization.


Assuntos
Reabsorção Óssea/genética , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T/genética , Traumatismos da Medula Espinal/complicações , Linfócitos T/patologia , Animais , Densidade Óssea/genética , Densidade Óssea/imunologia , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/imunologia , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Reabsorção Óssea/imunologia , Reabsorção Óssea/metabolismo , Contagem de Células , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Antígenos de Linfócitos T alfa-beta/deficiência , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Microtomografia por Raio-X
3.
J Fish Biol ; 98(4): 1031-1038, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32383168

RESUMO

Immobilization, such as prolonged bed rest, is a risk factor for bone loss in humans. Motivated by the emerging utility of zebrafish (Danio rerio) as an animal of choice for the study of musculoskeletal disease, here we report a model of restricted mobility induced osteopenia in adult zebrafish. Aquatic tanks with small cubical compartments to restrict the movement and locomotion of single fish were designed and fabricated for this study. Adult zebrafish were divided into two groups: a normal control (CONT) and a restricted mobility group (RMG) (18 fish/group). Six fish from each group were euthanized on days 14, 21 and 35 of the movement restriction. By using microcomputed tomography (micro-CT), we assessed bone volume/tissue volume (BV/TV) and bone density in the whole skeleton of the fish. Furthermore, we assessed skeletal shape in the vertebrae (radius, length, volume, neural and haemal arch aperture areas, neural and haemal arch angle, and thickness of the intervertebral space), single vertebra bone volume and bone density. Movement restriction significantly decreased vertebral skeletal parameters such as radius, length, volume, arch aperture areas and angles as well as the thickness of the intervertebral space in RMG. Furthermore, restricted mobility significantly (P < 0.001) decreased BV/TV and bone density as compared to the CONT group, starting as early as 14 days. By analysing zebrafish from CONT and RMG, we show that micro-CT imaging is a sensitive method to quantify distinct skeletal properties in zebrafish. We further defined the micro-CT parameters which can be used to examine the effects of restricted mobility on the skeleton of the fish. Our findings propose a rapid and effective osteopenia "stabulation" model, which could be used widely for osteoporosis drug screening.


Assuntos
Doenças Ósseas Metabólicas/patologia , Limitação da Mobilidade , Animais , Densidade Óssea/efeitos dos fármacos , Osso e Ossos , Modelos Animais de Doenças , Osteoporose , Coluna Vertebral , Microtomografia por Raio-X/métodos , Peixe-Zebra
4.
Mol Biol Rep ; 48(1): 969-974, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33289909

RESUMO

Haemophilic arthropathy (HA), caused by intra-articular haemorrhage, is one of the most common complications in patients with haemophilia. Factor replacement therapy provides missing coagulation factors to prevent children with haemophilia from joint bleeding and decreases their risk for HA. However, haemophilia patients in developing countries are still suffering from HA due to insufficient replacement therapy. Symptoms such as pain and activity limitations caused by HA seriously affect the functional abilities and quality of life of patients with HA, causing a high disability rate in the haemophilia cohort. The pathological mechanism of HA is complicated because the whole pathological mainly involves hypertrophic synovitis, osteopenia, cartilage and bone destruction, and these pathological changes occur in parallel and interact with each other. Inflammation plays an important role in the whole complex pathological process, and iron, cytokines, growth factors and other factors are involved. This review summarizes the pathological mechanism of HA to provide background for clinical and basic research.


Assuntos
Artrite/patologia , Doenças Ósseas Metabólicas/patologia , Hemartrose/patologia , Hemofilia A/patologia , Osteonecrose/patologia , Sinovite/patologia , Adulto , Artrite/genética , Artrite/imunologia , Artrite/metabolismo , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/imunologia , Doenças Ósseas Metabólicas/metabolismo , Criança , Citocinas/genética , Citocinas/imunologia , Fator VIII/uso terapêutico , Regulação da Expressão Gênica , Hemartrose/genética , Hemartrose/imunologia , Hemartrose/metabolismo , Hemofilia A/genética , Hemofilia A/imunologia , Hemofilia A/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Ferro/imunologia , Ferro/metabolismo , Articulações/imunologia , Articulações/metabolismo , Articulações/patologia , Osteonecrose/genética , Osteonecrose/imunologia , Osteonecrose/metabolismo , Qualidade de Vida , Sinovite/genética , Sinovite/imunologia , Sinovite/metabolismo
5.
Nephrol Dial Transplant ; 36(4): 722-729, 2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33367861

RESUMO

BACKGROUND: Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear. METHODS: This nested case-control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively. RESULTS: A landmark analysis demonstrated that death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P < 0.001). In the nested case-control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio = 0.38; 95% confidence interval 0.30-0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use >1 year and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments. CONCLUSIONS: Bisphosphonates may improve long-term graft survival in kidney transplant recipients.


Assuntos
Doenças Ósseas Metabólicas/tratamento farmacológico , Difosfonatos/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Osteoporose/tratamento farmacológico , Adulto , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Masculino , Osteoporose/etiologia , Osteoporose/patologia , Taxa de Sobrevida , Transplantados
6.
Front Endocrinol (Lausanne) ; 11: 588773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162940

RESUMO

Immobilization results in a substantial bone loss and increased fracture risk. Powerful bone anabolic therapies are necessary to counteract the bone loss and reduce fracture risk during periods with immobilization. Intermittent parathyroid hormone 1-34 (PTH) (teriparatide) and PTH related peptide analog abaloparatide (ABL) are potent bone anabolic therapies acting through the same receptor, but induce different durations of signaling response. We investigated the efficacy of PTH or ABL in preventing immobilization-induced bone loss in rats in a direct mole-to-mole comparison. Immobilization was achieved by injecting botulinum toxin type A (BTX) into the right hindlimb musculature. Sixty 14-week-old female Wistar rats were allocated to the following groups: Baseline, Control, BTX, BTX + PTH (80 µg/kg/day), and BTX + ABL (77 µg/kg/day). Immobilization resulted in a substantial and significant reduction in bone mineral density (aBMD), metaphyseal and epiphyseal trabecular bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), metaphyseal trabecular number (Tb.N), and femoral neck bone strength. Both PTH and ABL prevented the immobilization-induced decrease in aBMD, metaphyseal and epiphyseal Tb.Th, and metaphyseal Tb.N. In addition, PTH rescued the reduction in metaphyseal BV/TV and femoral neck strength, while ABL did not. However, the effect of PTH and ABL did not differ significantly for serum calcium, aBMD, metaphyseal, and epiphyseal BV/TV, Tb.Th, or Tb.N. In conclusion, in a mole-to-mole comparison the efficacy of PTH and ABL is similar in counteracting immobilization-induced reduction in bone mineral density, deterioration in trabecular microarchitecture, and decrease in bone strength.


Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Imobilização/efeitos adversos , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Hormônio Paratireóideo/farmacologia , Animais , Fenômenos Biomecânicos , Conservadores da Densidade Óssea/farmacologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/patologia , Hormônios e Agentes Reguladores de Cálcio/farmacologia , Feminino , Ratos , Ratos Wistar
7.
Oxid Med Cell Longev ; 2020: 6080597, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194005

RESUMO

Objectives. Quercetin (Q) and its derivatives are the major members of the naturally occurring flavonoid family, which possess beneficial effects on disease prevention including osteoporosis. The present study is aimed at further investigating the efficacy of the Q and its derivatives on bone pathology, bone-related parameters under imageology, bone maximum load, and serum bone metabolism indexes in animal model of osteoporosis. Potential mechanisms of Q and its derivatives in the treatment of osteoporosis as well as the existing problems regarding the modeling method and limitations of researches in this area were also summarized. Eight databases were searched from their inception dates to February 2020. Nineteen eligible studies containing 21 comparisons were identified ultimately. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. The results displayed the number of criteria met varied from 3/10 to 7/10 with an average of 5.05. The present study provided the preliminary preclinical evidence that oral administration of Q or its derivatives was capable of improving bone pathology, bone-related parameters under imageology and bone maximum load, increasing serum osteocalcin, alkaline phosphatase, and estradiol, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P < 0.05). No statistical difference was seen in survival rate, index of liver, or kidney function (P > 0.05). Q and its derivatives partially reverse osteopenia probably via antioxidant, anti-inflammatory, promoting osteogenesis, inhibiting osteoclasts, and its estrogen-like effect. The findings reveal the possibility of developing Q or its derivatives as a drug or an ingredient in diet for clinical treatment of osteoporosis.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Quercetina , Administração Oral , Animais , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Modelos Animais de Doenças , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/patologia , Quercetina/análogos & derivados , Quercetina/uso terapêutico
8.
Sci Rep ; 10(1): 15079, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934295

RESUMO

Osteoarthritis (OA) leads to joint pain from intraarticular inflammation with articular cartilage erosion, deterioration of joint function and abnormal subchondral bone structure. Besides aging, chronic repetitive joint injury is a common risk factor in young individuals. Nevertheless, whether OA is associated with bone loss at other skeletal sites is unclear. Since OA-associated proinflammatory cytokines-some of which are osteoclastogenic factors-are often detected in the circulation, we hypothesized that the injury-induced knee OA could result in widespread osteopenia at bone sites distant to the injured knee. Here we performed anterior cruciate ligament transection (ACLT) to induce knee OA in one limb of female Sprague-Dawley rats and determined bone changes post-OA induction by micro-computed tomography and computer-assisted bone histomorphometry. We found that although OA modestly altered bone density, histomorphometric analyses revealed increases in bone resorption and osteoid production with impaired mineralization. The bone formation rate was also reduced in OA rats. In conclusions, ACLT in young growing rats induced microstructural defects in the trabecular portion of weight-bearing (tibia) and non-weight-bearing bones (L5 vertebra), in part by enhancing bone resorption and suppressing bone formation. This finding supports the increasing concern regarding the repetitive sport-related ACL injuries and the consequent bone loss.


Assuntos
Doenças Ósseas Metabólicas/patologia , Calcificação Fisiológica/fisiologia , Articulação do Joelho/patologia , Osteoartrite do Joelho/patologia , Tíbia/patologia , Animais , Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/patologia , Artralgia/patologia , Reabsorção Óssea/patologia , Cartilagem Articular/patologia , Condrócitos/patologia , Modelos Animais de Doenças , Feminino , Traumatismos do Joelho/patologia , Masculino , Osteogênese/fisiologia , Ratos , Ratos Sprague-Dawley
9.
Cell Death Dis ; 11(9): 762, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938907

RESUMO

PKC-δ is an important molecule for B-cell proliferation and tolerance. B cells have long been recognized to play a part in osteoimmunology and pathological bone loss. However, the role of B cells with PKC-δ deficiency in bone homeostasis and the underlying mechanisms are unknown. We generated mice with PKC-δ deletion selectively in B cells by crossing PKC-δ-loxP mice with CD19-Cre mice. We studied their bone phenotype using micro-CT and histology. Next, immune organs were obtained and analyzed. Western blotting was used to determine the RANKL/OPG ratio in vitro in B-cell cultures, ELISA assay and immunohistochemistry were used to analyze in vivo RANKL/OPG balance in serum and bone sections respectively. Finally, we utilized osteoclastogenesis to study osteoclast function via hydroxyapatite resorption assay, and isolated primary calvaria osteoblasts to investigate osteoblast proliferation and differentiation. We also investigated osteoclast and osteoblast biology in co-culture with B-cell supernatants. We found that mice with PKC-δ deficiency in B cells displayed an osteopenia phenotype in the trabecular and cortical compartment of long bones. In addition, PKC-δ deletion resulted in changes of trabecular bone structure in association with activation of osteoclast bone resorption and decrease in osteoblast parameters. As expected, inactivation of PKC-δ in B cells resulted in changes in spleen B-cell number, function, and distribution. Consistently, the RANKL/OPG ratio was elevated remarkably in B-cell culture, in the serum and in bone specimens after loss of PKC-δ in B cells. Finally, in vitro analysis revealed that PKC-δ ablation suppressed osteoclast differentiation and function but co-culture with B-cell supernatant reversed the suppression effect, as well as impaired osteoblast proliferation and function, indicative of osteoclast-osteoblast uncoupling. In conclusion, PKC-δ plays an important role in the interplay between B cells in the immune system and bone cells in the pathogenesis of bone lytic diseases.


Assuntos
Linfócitos B/metabolismo , Doenças Ósseas Metabólicas/metabolismo , Reabsorção Óssea/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Proteína Quinase C-delta/deficiência , Ligante RANK/metabolismo , Animais , Linfócitos B/enzimologia , Linfócitos B/patologia , Doenças Ósseas Metabólicas/patologia , Reabsorção Óssea/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Osteoblastos/patologia , Osteoclastos/patologia , Ligante RANK/biossíntese , Regulação para Cima
10.
Artigo em Inglês | MEDLINE | ID: mdl-32982960

RESUMO

The human immunodeficiency virus type 1 (HIV)/AIDS pandemic represents the most significant global health challenge in modern history. This infection leads toward an inflammatory state associated with chronic immune dysregulation activation that tilts the immune-skeletal interface and its deep integration between cell types and cytokines with a strong influence on skeletal renewal and exacerbated bone loss. Hence, reduced bone mineral density is a complication among HIV-infected individuals that may progress to osteoporosis, thus increasing their prevalence of fractures. Highly active antiretroviral therapy (HAART) can effectively control HIV replication but the regimens, that include tenofovir disoproxil fumarate (TDF), may accelerate bone mass density loss. Molecular mechanisms of HIV-associated bone disease include the OPG/RANKL/RANK system dysregulation. Thereby, osteoclastogenesis and osteolytic activity are promoted after the osteoclast precursor infection, accompanied by a deleterious effect on osteoblast and its precursor cells, with exacerbated senescence of mesenchymal stem cells (MSCs). This review summarizes recent basic research data on HIV pathogenesis and its relation to bone quality. It also sheds light on HAART-related detrimental effects on bone metabolism, providing a better understanding of the molecular mechanisms involved in bone dysfunction and damage as well as how the HIV-associated imbalance on the gut microbiome may contribute to bone disease.


Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Doenças Ósseas Metabólicas/patologia , Infecções por HIV/complicações , Homeostase , Osteoporose/patologia , Doenças Ósseas Metabólicas/induzido quimicamente , HIV/efeitos dos fármacos , HIV/isolamento & purificação , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Osteoporose/induzido quimicamente
11.
Endocrinol Metab (Seoul) ; 35(2): 456-469, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32615730

RESUMO

BACKGROUND: We investigated RNA sequencing-based transcriptome profiling and the transformation of mature osteoblasts into bone lining cells (BLCs) through a lineage tracing study to better understand the effect of mechanical unloading on bone loss. METHODS: Dmp1-CreERt2(+):Rosa26R mice were injected with 1 mg of 4-hydroxy-tamoxifen three times a week starting at postnatal week 7, and subjected to a combination of botulinum toxin injection with left hindlimb tenotomy starting at postnatal week 8 to 10. The animals were euthanized at postnatal weeks 8, 9, 10, and 12. We quantified the number and thickness of X-gal(+) cells on the periosteum of the right and left femoral bones at each time point. RESULTS: Two weeks after unloading, a significant decrease in the number and a subtle change in the thickness of X-gal(+) cells were observed in the left hindlimbs compared with the right hindlimbs. At 4 weeks after unloading, the decrease in the thickness was accelerated in the left hindlimbs, although the number of labeled cells was comparable. RNA sequencing analysis showed downregulation of 315 genes in the left hindlimbs at 2 and 4 weeks after unloading. Of these, Xirp2, AMPD1, Mettl11b, NEXN, CYP2E1, Bche, Ppp1r3c, Tceal7, and Gadl1 were upregulated during osteoblastogenic/osteocytic and myogenic differentiation in vitro. CONCLUSION: These findings demonstrate that mechanical unloading can accelerate the transformation of mature osteoblasts into BLCs in the early stages of bone loss in vivo. Furthermore, some of the genes involved in this process may have a pleiotropic effect on both bone and muscle.


Assuntos
Biomarcadores/análise , Doenças Ósseas Metabólicas/patologia , Diferenciação Celular , Elevação dos Membros Posteriores/métodos , Osteoblastos/citologia , Osteogênese , Transcriptoma , Animais , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Análise de Sequência de RNA
12.
J Clin Endocrinol Metab ; 105(9)2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32614948

RESUMO

CONTEXT: Osteosarcopenia (loss of skeletal muscle and bone mass and/or function usually associated with aging) shares pathophysiological mechanisms with polycystic ovary syndrome (PCOS). However, the relationship between osteosarcopenia and PCOS remains unclear. OBJECTIVE: We evaluated skeletal muscle index% (SMI% = [appendicular muscle mass/weight (kg)] × 100) and bone mineral density (BMD) in PCOS (hyperandrogenism + oligoamenorrhea), and contrasted these musculoskeletal markers against 3 reproductive phenotypes (i): HA (hyperandrogenism + eumenorrhea) (ii); OA (normoandrogenic + oligoamenorrhea) and (iii), controls (normoandrogenic + eumenorrhea). Endocrine predictors of SMI% and BMD were evaluated across the groups. DESIGN, SETTING, AND PARTICIPANTS: Multicenter case-control study of 203 women (18-48 years old) in New York State. RESULTS: PCOS group exhibited reduced SMI% (mean [95% confidence interval (CI)]; 26.2% [25.1,27.3] vs 28.8% [27.7,29.8]), lower-extremity SMI% (57.6% [56.7,60.0] vs 62.5% [60.3,64.6]), and BMD (1.11 [1.08,1.14] vs 1.17 [1.14,1.20] g/cm2) compared to controls. PCOS group also had decreased upper (0.72 [0.70,0.74] vs 0.77 [0.75,0.79] g/cm2) and lower (1.13 [1.10,1.16] vs 1.19 [1.16,1.22] g/cm2) limb BMD compared to HA. Matsuda index was lower in PCOS vs controls and positively associated with SMI% in all groups (all Ps ≤ 0.05). Only controls showed associations between insulin-like growth factor (IGF) 1 and upper (r = 0.84) and lower (r = 0.72) limb BMD (all Ps < 0.01). Unlike in PCOS, IGF-binding protein 2 was associated with SMI% in controls (r = 0.45) and HA (r = 0.67), and with upper limb BMD (r = 0.98) in HA (all Ps < 0.05). CONCLUSIONS: Women with PCOS exhibit early signs of osteosarcopenia when compared to controls likely attributed to disrupted insulin function. Understanding the degree of musculoskeletal deterioration in PCOS is critical for implementing targeted interventions that prevent and delay osteosarcopenia in this clinical population.


Assuntos
Doenças Ósseas Metabólicas/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Sarcopenia/epidemiologia , Adolescente , Adulto , Composição Corporal/fisiologia , Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Estudos de Casos e Controles , Feminino , Indicadores Básicos de Saúde , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Fatores de Risco , Sarcopenia/etiologia , Sarcopenia/metabolismo , Sarcopenia/patologia , Adulto Jovem
13.
Phytother Res ; 34(11): 3029-3040, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32510717

RESUMO

Securinine (Sec) is a naturally derived compound separated from the roots of Securinega suffruticosa, which has long been used as a herbal medicine. Sec is widely known as a GABA receptor antagonist, it is also known as an innate immune cell agonist and has been reported to increase macrophage activity and promote monocyte maturation. On the basis of these studies, we investigated the effect of Sec on osteoclast differentiation and bone resorbing function. We have found that Sec inhibits RANKL-induced osteoclast differentiation, fusion, actin ring formation, and bone resorbing function by the inhibition of gene expression associated with each stage. Moreover, Sec significantly suppressed osteoclastogenesis by decreasing the phosphorylation of p38, Akt, JNK, IκB, and PLCγ2, in pathways involved in early osteoclastogenesis as well as through the subsequent suppression of c-Fos and NFATc1. Finally, Sec effectively protected bone loss induced by the excessive inflammatory responses and activity of osteoclasts in vivo by a micro-CT and histological analysis. In conclusion, our findings suggest that Sec may be a promising drug for bone metabolic diseases such as osteoporosis, which is associated with the excessive activity of osteoclasts.


Assuntos
Azepinas/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Medicina Herbária/métodos , Compostos Heterocíclicos de Anel em Ponte/uso terapêutico , Lactonas/uso terapêutico , Osteogênese/efeitos dos fármacos , Piperidinas/uso terapêutico , Animais , Azepinas/farmacologia , Doenças Ósseas Metabólicas/patologia , Diferenciação Celular , Compostos Heterocíclicos de Anel em Ponte/farmacologia , Humanos , Lactonas/farmacologia , Camundongos , Piperidinas/farmacologia
14.
Sci Rep ; 10(1): 7937, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404873

RESUMO

The objective of this study is to identify whether oxytocin (OT) contributes to the reduction of osteopenia in the femoral neck of rats in periestropause. Animals in irregular estrous cycles received two NaCl injections (0.15 mol/L) or OT (134 µg/kg) over a 12-h interval, and after thirty-five days without treatments, the biological sample collection was performed. The oxytocin group (Ot) demonstrated the highest enzymatic activity of alkaline phosphatase (p = 0.0138), lowest enzymatic activity of tartrate-resistant acid phosphatase (p = 0.0045), higher percentage of compact bone (p = 0.0359), cortical expression of runt-related transcription factor 2 (p = 0.0101), osterix (p = 0.0101), bone morphogenetic protein-2/4 (p = 0.0101) and periostin (p = 0.0455). Furthermore, the mineral-to-matrix ratio (ν1PO4/Proline) was higher and type-B carbonate substitution (CO3/ν1PO4) was lower (p = 0.0008 and 0.0303) in Ot group. The Ot showed higher areal bone mineral density (p = 0.0050), cortical bone area (p = 0.0416), polar moment of inertia, maximum, minimum (p = 0.0480, 0.0480, 0.0035), bone volume fraction (p = 0.0166), connectivity density (p < 0.0001), maximal load (p = 0.0003) and bone stiffness (p = 0.0145). In Ot percentage of cortical pores (p = 0.0102) and trabecular number (p = 0.0088) was lower. The results evidence action of OT in the reduction of osteopenia, suggesting that it is a promising anabolic strategy for the prevention of primary osteoporosis during the periestropause period.


Assuntos
Densidade Óssea , Colo do Fêmur/metabolismo , Colo do Fêmur/patologia , Ocitocina/metabolismo , Animais , Biomarcadores , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Modelos Animais de Doenças , Feminino , Colo do Fêmur/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/etiologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Ratos , Análise Espectral Raman , Microtomografia por Raio-X
15.
Cell Death Dis ; 11(5): 330, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382069

RESUMO

Quaking (QKI), an RNA-binding protein, has been reported to exhibit numerous biological functions, such as mRNA regulation, cancer suppression, and anti-inflammation. However, little known about the effects of QKI on bone metabolism. In this study, we used a monocyte/macrophage-specific QKI knockout transgenic mouse model to investigate the effects of QKI deficiency on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. The loss of QKI promoted the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) from bone marrow macrophages, and upregulated the expression of OC-specific markers, including TRAP (Acp5) and cathepsin K (Ctsk). The pro-osteoclastogenesis effect of QKI deficiency was achieved by amplifying the signaling cascades of the NF-κB and mitogen-activated protein kinase (MAPK) pathways; then, signaling upregulated the activation of nuclear factor of activated T cells c1 (NFATc1), which is considered to be the core transcription factor that regulates OC differentiation. In addition, QKI deficiency could inhibit osteoblast (OB) formation through the inflammatory microenvironment. Taken together, our data suggest that QKI deficiency promoted OC differentiation and disrupted bone metabolic balance, and eventually led to osteopenia under physiological conditions and aggravated the degree of osteoporosis under pathological conditions.


Assuntos
Osso e Ossos/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismo , Ligante RANK/farmacologia , Proteínas de Ligação a RNA/metabolismo , Animais , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Modelos Animais de Doenças , Feminino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Knockout , NF-kappa B/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/complicações , Osteoporose/patologia , Ovariectomia
16.
J Bone Miner Metab ; 38(5): 620-630, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32296985

RESUMO

INTRODUCTION: Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. This study aimed to compare bone morphological and mechanical properties of old and young sheep, and to evaluate the suitability of the old sheep as a model for senile osteopenia. MATERIALS AND METHODS: The lumbar vertebral body L3 of female merino sheep with two age ranges, i.e., old animals (6-10 years; n = 41) and young animals (2-4 years; n = 40), was analyzed concerning its morphological and mechanical properties by bone densitometry, quantitative histomorphometry, and biomechanical testing of the corticalis and/or central spongious region. RESULTS: In comparison with young sheep, old animals showed only marginally diminished bone mineral density of the vertebral bodies, but significantly decreased structural (bone volume, - 15.1%; ventral cortical thickness, - 11.8%; lateral cortical thickness, - 12.2%) and bone formation parameters (osteoid volume, osteoid surface, osteoid thickness, osteoblast surface, all - 100.0%), as well as significantly increased bone erosion (eroded surface, osteoclast surface). This resulted in numerically decreased biomechanical properties (compressive strength; - 6.4%). CONCLUSION: Old sheep may represent a suitable model of senile osteopenia with markedly diminished bone structure and formation, and substantially augmented bone erosion. The underlying physiological aging concept reduces challenging surgical procedures and ethical concerns and, due to complex alteration of different facets of bone turnover, may be well representative of the human condition.


Assuntos
Doenças Ósseas Metabólicas/patologia , Modelos Animais de Doenças , Ovinos/fisiologia , Animais , Fenômenos Biomecânicos , Densidade Óssea , Doenças Ósseas Metabólicas/fisiopatologia , Osso Esponjoso/patologia , Osso Esponjoso/fisiopatologia , Força Compressiva , Módulo de Elasticidade , Feminino , Vértebras Lombares/patologia , Vértebras Lombares/fisiopatologia , Osteogênese
17.
J Vet Med Sci ; 82(5): 536-540, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32238670

RESUMO

An osteoma is an infrequent tumor documented in avian species. An adult female Peach-Faced Lovebird (Agapornis roseicollis) with a history of previous trauma was examined due to the presence of bilateral hard and yellowish-white masses in the radio-cubital humerus junction. Histopathological dermal examination revealed a non-neoplastic process of mesenchymal origin, characterized by the formation of well-differentiated trabecular bone, multiple areas of medullary bone and loose connective tissue and coagulation of the necrosis foci. Based on the histological findings and the medical history, the masses were diagnosed as bilateral secondary osteoma cutis. To our knowledge, this is the first report of this pathology with an acute course in this exotic pet bird. The previous trauma could be the initiating cause.


Assuntos
Agapornis , Doenças das Aves/diagnóstico , Doenças Ósseas Metabólicas/veterinária , Ossificação Heterotópica/veterinária , Dermatopatias Genéticas/veterinária , Animais , Doenças das Aves/patologia , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/patologia , Feminino , Ossificação Heterotópica/diagnóstico , Ossificação Heterotópica/patologia , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/patologia
18.
An Bras Dermatol ; 95(3): 351-354, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32265056

RESUMO

Secondary osteoma cutis is a phenomenon that may occur in several conditions. When it occurs in a melanocytic nevus it is named osteonevus of Nanta, an event considered uncommon and characterized by the presence of bone formation adjacent or interposed with melanocytic cells. There are reports of its occurrence in various melanocytic lesions, being more frequently associated with intradermal nevus. We report a case of osteonevus of Nanta in combined nevus, possibly the first description of this association.


Assuntos
Doenças Ósseas Metabólicas/patologia , Nevo Intradérmico/patologia , Nevo Pigmentado/patologia , Ossificação Heterotópica/patologia , Dermatoses do Couro Cabeludo/patologia , Dermatopatias Genéticas/patologia , Neoplasias Cutâneas/patologia , Adulto , Doenças Ósseas Metabólicas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Melanócitos/patologia , Nevo Intradérmico/cirurgia , Nevo Pigmentado/cirurgia , Ossificação Heterotópica/cirurgia , Dermatoses do Couro Cabeludo/cirurgia , Dermatopatias Genéticas/cirurgia , Neoplasias Cutâneas/cirurgia
19.
Food Funct ; 11(4): 3201-3212, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32211683

RESUMO

Osteoporosis is a common chronic disease in the elderly population and in some domestic animals. Caged layer osteoporosis (CLO) is a common bone metabolism disease that was recently recommended as an ideal animal model for osteoporosis. This study aimed to investigate the therapeutic effect and mechanism of dietary icariin (ICA), the main bioactive component of the Chinese herb Epimedium, on low bone mineral density (BMD) in older caged laying hens. A total of 216, 54-week-old Lohmann pink-shell laying hens were allocated to three groups, comprising one control group and two treatment groups that were additionally supplied with 0.5 or 2.0 g kg-1 ICA. The results showed that dietary ICA significantly increased the femur BMD by 49.3% and the tibia BMD by 38.9%, improved the microstructure of bone tissue, decreased levels of the bone metabolism index, enhanced serum antioxidant capacity and regulated messenger RNA expression of bone-related genes. ICA-induced differential metabolites were clarified by using untargeted metabolomics assays. Furthermore, correlation analysis between differential metabolites and BMD indicated that eight differential metabolites correlated highly with both femur and tibia BMD, including uridine, taurine, palmitic acid, adrenic acid, fexofenadine, lysoPC(18 : 1), lysoPE(20 : 3/0 : 0) and 3-acetyl-11-keto-beta-boswellic acid. ICA mainly perturbed pyrimidine metabolism, taurine metabolism and lipid metabolism, which led to increased BMD in older caged laying hens. These findings revealed underlying therapeutic mechanisms of dietary ICA on low BMD, and provided reference metabolites for the early diagnosis of osteoporosis.


Assuntos
Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Metabolômica , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/patologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Galinhas , Dieta , Modelos Animais de Doenças , Epimedium/química , Feminino , Fêmur/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Osteoporose/tratamento farmacológico , RNA Mensageiro/metabolismo , Tíbia/efeitos dos fármacos , Tíbia/patologia
20.
Molecules ; 25(5)2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32151025

RESUMO

Osteopenia or osteoporosis occurs frequently in alcoholics and patients with alcoholic fatty liver disease. Methoxsalen (MTS), 8-methoxypsoralen, improved osteoporosis in ovariectomized and diabetic mouse models; however, its effects on alcohol-induced osteopenia and steatosis have not been reported. This study examined the effects of MTS on alcohol-induced bone loss and steatosis. Rats in the alcohol groups were fed a Liber-DeCarli liquid diet containing 36% of its calories as alcohol. MTS was at 0.005% in their diet, while alendronate (positive control; 500 µg/kg BW/day) was administered orally for eight weeks. The pair-fed group received the same volume of isocaloric liquid diet containing dextrin-maltose instead of alcohol as the alcohol control group consumed the previous day. In the alcohol-fed rats, the MTS and alendronate increased the bone volume density, bone surface density and trabecular number, while the bone specific surface, trabecular separation and structure model index were decreased in the tibia. MTS down-regulated tibial tartrate-resistant acid phosphatase 5 (TRAP) expression compared to the alcohol control group. MTS or alendronate prevented chronic alcohol-induced hepatic lipid accumulation and the triglyceride level in the alcohol-fed rats by decreasing the lipogenic enzyme activities and increasing the fatty acid oxidation enzyme activities. MTS reduced significantly the serum levels of alcohol, TRAP and tumor necrosis factor-α compared to the alcohol control group. Overall, these results suggest that MTS is likely to be an alternative agent for alcoholic osteopenia and hepatosteatosis.


Assuntos
Alcoolismo/complicações , Doenças Ósseas Metabólicas/etiologia , Suplementos Nutricionais , Fígado Gorduroso/etiologia , Metoxaleno/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biomarcadores , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/patologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/patologia , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...