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1.
J Med Life ; 14(2): 181-197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104241

RESUMO

The present study investigated the capacity of Suprathel® (a copolymer membrane, so far validated for skin regeneration) to also regenerate oral tissue - mucosa and bone, by comparing this biomaterial, in a split-mouth rabbit model, to Mucoderm®, a xenogeneic collagen matrix certified for keratinized oral mucosa healing. The clinical reason behind this experimental animal model was to determine whether the benefits of this advanced skin regeneration product (Suprathel®) could be conveyed for future evaluation in clinical trials of oral tissue regeneration in humans. The outcomes of this study validated the use of Suprathel®, a terpolymer of polylactide with trimethylene carbonate and ε-caprolactone, for stimulation of oral epithelium and alveolar bone regeneration in rabbits. Both Suprathel® and Mucoderm® exhibited comparable results and the null hypothesis stating a comparable regenerating effect of these two materials could not be rejected.


Assuntos
Osso e Ossos/patologia , Epitélio/patologia , Boca/fisiologia , Poliésteres/química , Regeneração , Cicatrização , Animais , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Osso Esponjoso/patologia , Regeneração Tecidual Guiada , Masculino , Mucosa Bucal/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Coelhos , Cicatrização/efeitos dos fármacos
2.
Toxins (Basel) ; 13(6)2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070555

RESUMO

Fumonisins (FB) are metabolites found in cereal grains (including maize), crop products, and pelleted feed. There is a dearth of information concerning the effects of FB intoxication on the intestinal histomorphometry, the expression of intestinal tight junction proteins, and the bone structure and liver in pre-laying hens. The current experiment was carried out on hens from the 11th to the 14th week of age. The hens were orally administered an extract containing fumonisin B1 (FB1) and fumonisin B2 (FB2) at doses of 0.0 mg/kg b.w. (body weight), 1.0 mg/kg b.w., 4.0 mg/kg b.w., and 10.9 mg/kg b.w. for 21 days. Following FB intoxication, the epithelial integrity of the duodenum and jejunum was disrupted, and dose-dependent degenerative changes were observed in liver. An increased content of immature collagen was observed in the bone tissue of FB-intoxicated birds, indicating intensified bone turnover. A similar effect was observed with regards to the articular cartilage, where enhanced fibrillogenesis was observed mainly in the group of birds that received the FB extract at a dose of 10.9 mg/kg b.w. In conclusion, FB intoxication resulted in negative structural changes in the bone tissue of the hens, which could result in worsened bone mechanics and an increase in the risk of bone fractures. Fumonisin administration, even at a dose of 1.0 mg/kg b.w., can lead to degradation of the intestinal barrier and predispose hens to intestinal disturbances later in life.


Assuntos
Osso e Ossos/efeitos dos fármacos , Fumonisinas/envenenamento , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Proteínas de Junções Íntimas/análise , Administração Oral , Animais , Osso e Ossos/patologia , Galinhas , Feminino , Intestinos/química , Intestinos/patologia , Fígado/patologia
3.
Hum Genet ; 140(8): 1121-1141, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34169326

RESUMO

Osteogenesis Imperfecta (OI) comprises a heterogeneous group of patients who share bone fragility and deformities as the main characteristics, albeit with different degrees of severity. Phenotypic variation also exists in other connective tissue aspects of the disease, complicating disease classification and disease course prediction. Although collagen type I defects are long established as the primary cause of the bone pathology, we are still far from comprehending the complete mechanism. In the last years, the advent of next generation sequencing has triggered the discovery of many new genetic causes for OI, helping to draw its molecular landscape. It has become clear that, in addition to collagen type I genes, OI can be caused by multiple proteins connected to different parts of collagen biosynthesis. The production of collagen entails a complex process, starting from the production of the collagen Iα1 and collagen Iα2 chains in the endoplasmic reticulum, during and after which procollagen is subjected to a plethora of posttranslational modifications by chaperones. After reaching the Golgi organelle, procollagen is destined to the extracellular matrix where it forms collagen fibrils. Recently discovered mutations in components of the retrograde transport of chaperones highlight its emerging role as critical contributor of OI development. This review offers an overview of collagen regulation in the context of recent gene discoveries, emphasizing the significance of transport disruptions in the OI mechanism. We aim to motivate exploration of skeletal fragility in OI from the perspective of these pathways to identify regulatory points which can hint to therapeutic targets.


Assuntos
Osso e Ossos/metabolismo , Colágeno Tipo I/biossíntese , Osteoblastos/metabolismo , Osteogênese Imperfeita/metabolismo , Pró-Colágeno/biossíntese , Processamento de Proteína Pós-Traducional , Osso e Ossos/patologia , Colágeno Tipo I/genética , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Complexo de Golgi/genética , Complexo de Golgi/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Mutação , Osteoblastos/patologia , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia , Pró-Colágeno/genética , Biossíntese de Proteínas , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Transporte Proteico , Índice de Gravidade de Doença
4.
Acta Orthop Traumatol Turc ; 55(3): 239-245, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34100365

RESUMO

OBJECTIVE: The aim of this study was to compare the effect of Gap Balancing (GB) versus Measured Resection (MR) techniques on the early clinical and radiological results of Total Knee Arthroplasty (TKA). METHODS: In this prospective study, 99 patients (99 knees) who underwent unilateral TKA between March 2018 and January 2019 were randomly allocated to one of two groups: The GP group, TKA with GB technique (19 male, 31 female; mean age = 55.9 ±16.5) and the MR group, TKA with MR technique (19 male, 30 female; mean age = 54.2 ± 18.7). Patients in both groups were comparable in terms of the demographic and clinical data. The angle of cutting block to PCA and Cutting Thickness of the Medial and Lateral Condyle (CTMC, CTLC) were intraoperatively measured. In radiographic analysis, Preoperative Mechanical Femorotibial Angle (Pre-mFTA), Postoperative Mechanical Femorotibial Angle (Post-mFTA), and joint line changes were examined. Femoral component Rotation Angle (FCRA) was also measured by computed tomography. In gait analysis, the spatiotemporal parameters (walking speed, step length, and single support time) and kinematics parameters (flexion angle, extension angle, and transversal rotation) were collected at 12 months postoperatively. Furthermore, Western Ontario and McMaster Universities Arthritis Index (WOMAC) were performed at 12 months after surgery. RESULTS: CTMC and CTLC were both significantly higher in GB group than in the MR group (9.8±2.0 mm vs 8.5 ± 1.2 mm; 7.9 ± 1.8mm vs 6.8 ± 1.4mm; P = 0.001, P = 0.002, respectively). Angle of cutting block to PCA was statistically lower in GB group than in the MR group (1.7 ± 1.5° vs 3.1 ± 0.5 °; P < 0.001). FCRA is greater in the GB group compared to the MR group, but the difference did not reach statistical significance (1.2 ± 2.8 ° vs 0.7 ± 2.0 °; P > 0.05). Although post-mFTA significantly improved compared with pre-mFTA in both groups, no significant difference was observed in the changes of post-mFTA between the two groups (0.9 ± 1.7° vs 0.3 ± 1.8°, P > 0.05). No significant differences were determined between the two groups in spatiotemporal gait parameters including walking speed, step length, and single support time. The sagittal max knee flexion range was significantly larger in the GB group than in the MR group (49.27 ± 5.24 ° vs 45.99 ± 8.21 °, P < 0.05). The flexion range did not reach the level of the control group. There was no significant difference between the two groups in WOMAC at 12 months follow-up (P > 0.05). CONCLUSION: Evidence from this study has revealed GB and MR techniques have both little effect on early clinical results of TKA. Nonetheless, GB technique can provide better knee flexion in the early postoperative gait status compared with MR technique. LEVEL OF EVIDENCE: Level I, Therapeutic Study.


Assuntos
Artroplastia do Joelho , Osso e Ossos , Articulação do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Pesos e Medidas Corporais/métodos , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Feminino , Análise da Marcha/métodos , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/cirurgia , Avaliação de Resultados em Cuidados de Saúde/métodos , Amplitude de Movimento Articular , Análise Espaço-Temporal , Tomografia Computadorizada por Raios X/métodos
5.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066978

RESUMO

Bone and muscle are highly synergistic tissues that communicate extensively via mechanotransduction and biochemical signaling. Osteogenesis imperfecta (OI) is a heritable connective tissue disorder of severe bone fragility and recently recognized skeletal muscle weakness. The presence of impaired bone and muscle in OI leads to a continuous cycle of altered muscle-bone crosstalk with weak muscles further compromising bone and vice versa. Currently, there is no cure for OI and understanding the pathogenesis of the skeletal muscle weakness in relation to the bone pathogenesis of OI in light of the critical role of muscle-bone crosstalk is essential to developing and identifying novel therapeutic targets and strategies for OI. This review will highlight how impaired skeletal muscle function contributes to the pathophysiology of OI and how this phenomenon further perpetuates bone fragility.


Assuntos
Osso e Ossos/patologia , Debilidade Muscular/patologia , Músculo Esquelético/patologia , Osteogênese Imperfeita/patologia , Animais , Fenômenos Biomecânicos , Osso e Ossos/fisiopatologia , Metabolismo Energético , Humanos , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Osteogênese Imperfeita/metabolismo , Osteogênese Imperfeita/fisiopatologia
6.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067582

RESUMO

Osteosarcopenia, the coexistence of bone and muscle loss, is common in older adults, but its definition lacks international consensus. This cross-sectional study (n = 1199 post-menopausal women) aimed to determine the association between osteosarcopenia and fragility fractures and to investigate the impact of the definition of the "osteo" component. Bone mineral density and bone microarchitecture were measured by dual-energy X-ray absorptiometry and the trabecular bone score (TBS), respectively. The "osteo" component of osteosarcopenia was classified as osteoporosis (T-score ≤ -2.5 SD), osteopenia/osteoporosis (T-score < -1 SD), and high-fracture-risk osteopenia (-2.5 SD < T-score < -1 SD)/osteoporosis (T-score ≤ -2.5 SD). The Fracture Risk Assessment Tool was used to identify high-fracture-risk osteopenia. Altogether, 30.3%, 32.2%, 14.4%, and 23.1% of participants had osteosarcopenia, osteoporosis alone, sarcopenia alone, and neither condition, respectively. The odds ratios between osteosarcopenia and fragility fractures were 3.70 (95% CI: 1.94-7.04) for osteosarcopenia, 2.48 (95% CI: 1.30-4.71) for osteoporosis alone, and 1.87 (95% CI: 0.84-4.14) for sarcopenia alone. Women with osteosarcopenia also had lower TBS, indicating worse bone microarchitecture. In conclusion, women with osteosarcopenia were more likely to have previously sustained a fracture compared to those without osteosarcopenia, with sarcopenia alone, and with osteoporosis alone. The relationship between osteosarcopenia and fracture risk may be best identified when considering high-fracture-risk osteopenia and osteoporosis.


Assuntos
Doenças Ósseas Metabólicas/fisiopatologia , Sarcopenia/fisiopatologia , Absorciometria de Fóton , Idoso , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/metabolismo , Osso e Ossos/patologia , Osso Esponjoso , Estudos Transversais , Feminino , Fraturas Ósseas/etiologia , Fraturas Ósseas/metabolismo , Humanos , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Pós-Menopausa , Sarcopenia/complicações , Sarcopenia/metabolismo , Fraturas da Coluna Vertebral
7.
Aging (Albany NY) ; 13(10): 14342-14354, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34016788

RESUMO

There are few studies on the mechanism of pituitary adenoma (PA) destroying bone. The current study aimed to investigate the role of MEG8/miR-454-3p/TNF-α in bone-invasive pituitary adenomas (BIPAs). In this study, we report that lncRNA MEG8 and TNF-α are upregulated in BIPA tissues while miR-454-3p is downregulated, which is associated with poor progression-free survival (PFS). Functional assays revealed the role of up-regulated MEG8 and down-regulated miR-454-3p in promoting bone destruction. Mechanistically, MEG8 promotes TNF-α expression by sponging miR-454-3p, which ultimately leads to the occurrence of bone destruction. The mechanism is confirmed in vivo and in vitro. Therefore, our data illustrated a new regulatory mechanism of MEG8/miR-454-3p/TNF-α in BIPAs. It may provide a useful strategy for diagnosis and treatment for BIPA patients.


Assuntos
Adenoma/genética , Adenoma/patologia , Osso e Ossos/patologia , MicroRNAs/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , RNA Longo não Codificante/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Animais , Sequência de Bases , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Modelos Biológicos , Invasividade Neoplásica , Prognóstico , Células RAW 264.7 , RNA Longo não Codificante/genética , Regulação para Cima/genética
8.
Cell Prolif ; 54(7): e13043, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34008897

RESUMO

OBJECTIVES: Large bone defects are a common, debilitating clinical condition that have substantial global health and economic burden. Bone tissue engineering technology has become one of the most promising approaches for regenerating defective bones. In this study, we fabricated a naringin-inlaid composite silk fibroin/hydroxyapatite (NG/SF/HAp) scaffold to repair bone defects. MATERIALS AND METHODS: The salt-leaching technology was used to fabricate the NG/SF/HAp scaffold. The cytocompatibility of the NG/SF/HAp scaffold was assessed using scanning electron microscopy, live/dead cell staining and phalloidin staining. The osteogenic and angiogenic properties were assessed in vitro and in vivo. RESULTS: The porous NG/SF/HAp scaffold had a well-designed biomimetic porous structure with osteoinductive and angiogenic activities. A gene microarray identified 854 differentially expressed genes between human umbilical cord-derived mesenchymal stem cells (hUCMSCs) cultured on SF-nHAp scaffolds and cells cultured on NG/SF/HAp scaffolds. The underlying osteoblastic mechanism was investigated using hUCMSCs in vitro. Naringin facilitated hUCMSC ingrowth into the SF/HAp scaffold and promoted osteogenic differentiation. The osteogenic and angiogenic capabilities of cells cultured in the NG/SF/HAp scaffold were superior to those of cells cultured in the SF/HAp scaffold. CONCLUSIONS: The data indicate the potential of the SF/HAp composite scaffold incorporating naringin for bone regeneration.


Assuntos
Regeneração Óssea , Durapatita/química , Fibroínas/química , Flavanonas/química , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Osso e Ossos/patologia , Diferenciação Celular/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Porosidade , Coelhos , Engenharia Tecidual , Cordão Umbilical/citologia
9.
Cell Prolif ; 54(6): e13035, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33939201

RESUMO

OBJECTIVES: Adiponectin signalling has been considered to be a promising target to treat diabetes-related osteoporosis. However, contradictory results regarding bone formation were observed due to the various isoforms of adiponectin. Therefore, it would be necessary to investigate the effect of adiponectin receptor signals in regulating bone-fat balance. MATERIALS AND METHODS: We primarily applied a newly found specific activator for adiponectin receptor, AdipoRon, to treat bone metabolism-related cells to investigate the role of Adiponectin receptor signals on bone-fat balance. We then established femur defect mouse model and treated them with AdipoRon to see whether adiponectin receptor activation could promote bone regeneration. RESULTS: We found that AdipoRon could slightly inhibit the proliferation of pre-osteoblast and pre-osteoclast, but AdipoRon showed no effect on the viability of mesenchymal stromal cells. AdipoRon could remarkably promote cell migration of mesenchymal stromal cells. Additionally, AdipoRon promoted osteogenesis in both pre-osteoblasts and mesenchymal cells. Besides, AdipoRon significantly inhibited osteoclastogenesis via its direct impact on pre-osteoclast and its indirect inhibition of RANKL in osteoblast. Moreover, mesenchymal stromal stems cells showed obviously decreased adipogenesis when treated with AdipoRon. Consistently, AdipoRon-treated mice showed faster bone regeneration and repressed adipogenesis. CONCLUSIONS: Our study demonstrated a pro-osteogenic, anti-adipogenic and anti-osteoclastogenic effect of adiponectin receptor activation in young mice, which suggested adiponectin receptor signalling was involved in bone regeneration and bone-fat balance regulation.


Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/lesões , Gorduras/metabolismo , Osteogênese/efeitos dos fármacos , Piperidinas/farmacologia , Receptores de Adiponectina/agonistas , Células 3T3 , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Células Cultivadas , Modelos Animais de Doenças , Masculino , Camundongos , Piperidinas/uso terapêutico , Ratos Sprague-Dawley , Receptores de Adiponectina/metabolismo
10.
Molecules ; 26(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947088

RESUMO

This study examined for the first time whether bee bread (BB, consisting of monofloral rape bee pollen) could alleviate lipid derangements and reduced bone quality in Zucker diabetic fatty (ZDF) rats, which are considered an appropriate animal model for type 2 diabetes mellitus (T2DM) investigation. Adult ZDF rats were segregated into four groups: lean non-diabetic rats (L group), obese diabetic rats untreated (C group), and those treated with the BB at two doses (500 and 700 mg/kg body weight, respectively, B1 and B2 groups) for 10 weeks. Significantly reduced levels of total cholesterol and triglyceride were recorded in the B2 group versus the C group. In both BB-treated groups, significantly increased relative volume of trabecular bone and trabecular thickness, enhanced density of secondary osteons, accelerated periosteal bone apposition, and improved blood flow were observed. A positive effect of higher dose of BB on femoral weight and cortical bone thickness was also demonstrated. Our results suggest a promising potential of BB to ameliorate T2DM-related complications associated with lipid and bone damages.


Assuntos
Ração Animal , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Lipídeos/sangue , Obesidade/metabolismo , Obesidade/patologia , Própole/administração & dosagem , Animais , Biomarcadores , Osso e Ossos/diagnóstico por imagem , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Masculino , Obesidade/sangue , Obesidade/etiologia , Ratos , Ratos Zucker , Microtomografia por Raio-X
11.
J Parasitol ; 107(2): 275-283, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33844838

RESUMO

Parasitism is inherent to life and observed in all species. Extinct animals have been studied to understand what they looked like, where and how they lived, what they fed on, and the reasons they became extinct. Paleoparasitology helps to clarify these questions based on the study of the parasites and microorganisms that infected those animals, using as a source material coprolites, fossils in rock, tissue, bone, mummy, and amber, analyses of ancient DNA, immunodiagnosis, and microscopy.


Assuntos
Extinção Biológica , Fósseis/parasitologia , Sedimentos Geológicos/parasitologia , Paleopatologia , Doenças Parasitárias em Animais/história , Âmbar , Animais , Osso e Ossos/microbiologia , Osso e Ossos/parasitologia , Osso e Ossos/patologia , História Antiga , Múmias/parasitologia
12.
Nat Commun ; 12(1): 2174, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846342

RESUMO

Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvß3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.


Assuntos
Apoptose , Artrite Reumatoide/patologia , Inflamação/patologia , Articulações/patologia , Macrófagos/patologia , Osteoclastos/patologia , Animais , Artrite Reumatoide/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Endocitose/efeitos dos fármacos , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Articulações/diagnóstico por imagem , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Oligopeptídeos/química , Ratos , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologia , Distribuição Tecidual , Triterpenos , Microtomografia por Raio-X
13.
Clin Nucl Med ; 46(8): 688-690, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795591

RESUMO

ABSTRACT: Primary osseous B-lymphoblastic lymphoma/leukemia is very rare, especially multiple bones involved. Herein, we reported the bone scintigraphy findings in a 16-year-old adolescent boy with a 20-day history of right thigh pain caused by B-lymphoblastic lymphoma/leukemia. Multiple abnormal MDP-avid foci were noted on 99mTc-MDP bone scintigraphy. Interestingly, the CT images of corresponding lesions were unrevealing. Finally, the B-lymphoblastic lymphoma/leukemia was confirmed by pathology and immunohistochemistry.


Assuntos
Osso e Ossos/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico por imagem , Adolescente , Osso e Ossos/patologia , Humanos , Masculino , Cintilografia , Medronato de Tecnécio Tc 99m , Tomografia Computadorizada por Raios X
14.
Int J Mol Sci ; 22(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919677

RESUMO

Platelet-rich fibrin (PRF) is a natural fibrin meshwork material with multiple functions that are suitable for tissue engineering applications. PRF provides a suitable scaffold for critical-size bone defect treatment due to its platelet cytokines and rich growth factors. However, the structure of PRF not only promotes cell attachment but also, due to its density, provides a pool for cell migration into the PRF to facilitate regeneration. In our study, we used repeated freeze drying to enlarge the pores of PRF to engineer large-pore PRF (LPPRF), a type of PRF that has expanded pores for cell migration. Moreover, a biodegradable Mg ring was used to provide stability to bone defects and the release of Mg ions during degradation may enhance osteoconduction and osteoinduction. Our results revealed that cell migration was more extensive when LPPRF was used rather than when PRF was used and that LPPRF retained the growth factors present in PRF. Moreover, the Mg ions released from the Mg ring during degradation significantly enhanced the calcium deposition of MC3T3-E1 preosteoblasts. In the present study, a bone substitute comprising LPPRF combined with a Mg ring was demonstrated to have much potential for critical-size bone defect repair.


Assuntos
Osso e Ossos/patologia , Movimento Celular/efeitos dos fármacos , Magnésio/farmacologia , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Fibrina Rica em Plaquetas/metabolismo , Cicatrização , Animais , Osso e Ossos/efeitos dos fármacos , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/ultraestrutura , Coelhos , Tecidos Suporte/química , Titânio/farmacologia , Cicatrização/efeitos dos fármacos
15.
Biomed Res Int ; 2021: 6655225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928159

RESUMO

Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.


Assuntos
Exossomos/metabolismo , Necrose da Cabeça do Fêmur/prevenção & controle , Necrose da Cabeça do Fêmur/terapia , Cabeça do Fêmur/irrigação sanguínea , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica , Esteroides/efeitos adversos , Animais , Osso e Ossos/patologia , Hipóxia Celular , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Exossomos/ultraestrutura , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ratos Sprague-Dawley , Microtomografia por Raio-X
16.
Biomed Res Int ; 2021: 8872235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860056

RESUMO

Objective: To explore the effect and mechanism of the sponge dressing on the healing of refractory orthopedic wound, and the gelatin-Bletilla striata gum/Salvia miltiorrhiza nano Ag (GBS-Ag) sponge dressing was prepared. Methods: GBS-Ag sponge dressing was prepared by the freeze-drying method. Twenty male SD rats were randomly divided into the control group (Ctrl group) and GBS-Ag group, with 10 rats in each group, and the rats in the two groups were established a model of back wound infection. The Ctrl group was treated with gauze, while the GBS-Ag group was treated with GBS-Ag sponge dressing. Wound healing rate, blood immune indexes, Ag content in each organ, morphological changes of wound, and expression of transforming growth factor-ß1 (TGF-ß1) in wound transformation were detected in the two groups of rats. Results: The mechanical properties of GBS-Ag sponge dressing were all in line with the standard, and it had good killing effect on the conventional strain after being incubated for 24 hours. Compared with the Ctrl group, the healing rate and lymphocyte percentage in the GBS-Ag group were significantly increased on day 4 and day 10 (P < 0.05), while the total number of white blood cells and the percentage of neutrophils were significantly decreased (P < 0.05). Compared with Ctrl group, the Ag content in liver, spleen, and kidney of rats in the GBS-Ag group was significantly increased (P < 0.05). The histological results showed that the Ctrl group lacked collagen fibers in the dermis, and the angiogenesis was not rich, accompanied by a large number of inflammatory cell infiltration. The epidermal repair of rats in the GBS-Ag group was complete and partially keratinized, the dermis was rich in collagen fibers, with elastic fibers and new blood vessels, inflammatory cells were rare, and new hair follicles and thick-walled blood vessels were also observed. The expression of TGF-ß1 protein in the wounds of rats in the GBS-Ag group was higher than that of the Ctrl group. Conclusion: GBS-Ag sponge dressing had multiple effects of sterilization and promoting wound healing, and its mechanism may be related to promoting the TGF-ß1 protein expression.


Assuntos
Bandagens , Osso e Ossos/patologia , Gelatina/farmacologia , Nanopartículas/química , Orchidaceae/química , Poríferos/química , Salvia miltiorrhiza/química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Osso e Ossos/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Especificidade de Órgãos , Ratos Sprague-Dawley , Prata/farmacologia , Fator de Crescimento Transformador beta1/metabolismo
17.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805598

RESUMO

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following formation of a micrometastatic tumour mass by inhibiting metastatic processes including angiogenesis, bone remodeling and immunosuppressive cell functions. In this review we will highlight some of the mechanisms mediating DTC dormancy and the complex relationships which occur between tumor cells and bone resident cells in the bone metastatic microenvironment. These inter-cellular interactions may be important targets to consider for development of novel effective therapies for the prevention or treatment of bone metastases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/prevenção & controle , Regulação Neoplásica da Expressão Gênica , Neovascularização Patológica/prevenção & controle , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/genética , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/patologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/imunologia , Osso e Ossos/patologia , Comunicação Celular , Citocinas/genética , Citocinas/metabolismo , Humanos , Metástase Linfática , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/imunologia , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/imunologia , Osteoclastos/patologia , Transdução de Sinais , Evasão Tumoral/genética , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fatores de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/metabolismo
18.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805833

RESUMO

A large British study, with almost 3000 patients, identified diabetes as main risk factor for delayed and nonunion fracture healing, the treatment of which causes large costs for the health system. In the past years, much progress has been made to treat common complications in diabetics. However, there is still a lack of advanced strategies to treat diabetic bone diseases. To develop such therapeutic strategies, mechanisms leading to massive bone alterations in diabetics have to be well understood. We herein describe an in vitro model displaying bone metabolism frequently observed in diabetics. The model is based on osteoblastic SaOS-2 cells, which in direct coculture, stimulate THP-1 cells to form osteoclasts. While in conventional 2D cocultures formation of mineralized matrix is decreased under pre-/diabetic conditions, formation of mineralized matrix is increased in 3D cocultures. Furthermore, we demonstrate a matrix stability of the 3D carrier that is decreased under pre-/diabetic conditions, resembling the in vivo situation in type 2 diabetics. In summary, our results show that a 3D environment is required in this in vitro model to mimic alterations in bone metabolism characteristic for pre-/diabetes. The ability to measure both osteoblast and osteoclast function, and their effect on mineralization and stability of the 3D carrier offers the possibility to use this model also for other purposes, e.g., drug screenings.


Assuntos
Osso e Ossos/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Redes e Vias Metabólicas/genética , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osso e Ossos/patologia , Calcificação Fisiológica/genética , Anidrase Carbônica II/genética , Anidrase Carbônica II/metabolismo , Catepsina K/genética , Catepsina K/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Regulação da Expressão Gênica , Humanos , Modelos Biológicos , Osteoblastos/patologia , Osteoclastos/patologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , Células THP-1 , Fosfatase Ácida Resistente a Tartarato/genética , Fosfatase Ácida Resistente a Tartarato/metabolismo , Tecidos Suporte
19.
Nat Commun ; 12(1): 2046, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824347

RESUMO

Bone formation represents a heritable trait regulated by many signals and complex mechanisms. Its abnormalities manifest themselves in various diseases, including sclerosing bone disorder (SBD). Exploration of genes that cause SBD has significantly improved our understanding of the mechanisms that regulate bone formation. Here, we discover a previously unknown type of SBD in four independent families caused by bi-allelic loss-of-function pathogenic variants in TMEM53, which encodes a nuclear envelope transmembrane protein. Tmem53-/- mice recapitulate the human skeletal phenotypes. Analyses of the molecular pathophysiology using the primary cells from the Tmem53-/- mice and the TMEM53 knock-out cell lines indicates that TMEM53 inhibits BMP signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of BMP2-activated Smad proteins. Pathogenic variants in the patients impair the TMEM53-mediated blocking effect, thus leading to overactivated BMP signaling that promotes bone formation and contributes to the SBD phenotype. Our results establish a previously unreported SBD entity (craniotubular dysplasia, Ikegawa type) and contribute to a better understanding of the regulation of BMP signaling and bone formation.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Osso e Ossos/patologia , Proteínas de Membrana/metabolismo , Esclerose/patologia , Transdução de Sinais , Proteínas Smad/metabolismo , Animais , Sequência de Bases , Diferenciação Celular , Núcleo Celular/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos Mutantes , Mutação/genética , Osteoblastos/patologia , Linhagem , Fosforilação , Crânio/patologia , Adulto Jovem
20.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809315

RESUMO

Patients with advanced breast cancer are at high risk of developing bone metastasis. Despite treatment advances for primary breast cancer, metastatic bone disease remains incurable with a low relative survival. Hence, new therapeutic approaches are required to improve survival and treatment outcome for these patients. Bone is among the most frequent sites of metastasis in breast cancer. Once in the bone, disseminated tumor cells can acquire a dormant state and remain quiescent until they resume growth, resulting in overt metastasis. At this stage the disease is characterized by excessive, osteoclast-mediated osteolysis. Cells of the bone microenvironment including osteoclasts, osteoblasts and endothelial cells contribute to the initiation and progression of breast cancer bone metastasis. Direct cell-to-cell contact as well as soluble factors regulate the crosstalk between disseminated breast cancer cells and bone cells. In this complex signaling network interleukins (ILs) have been identified as key regulators since both, cancer cells and bone cells secrete ILs and express corresponding receptors. ILs regulate differentiation and function of bone cells, with several ILs being reported to act pro-osteoclastogenic. Consistently, the expression level of ILs (e.g., in serum) has been associated with poor prognosis in breast cancer. In this review we discuss the role of the most extensively investigated ILs during the establishment of breast cancer bone metastasis and highlight their potential as therapeutic targets in preventing metastatic outgrowth in bone.


Assuntos
Neoplasias Ósseas/genética , Neoplasias da Mama/genética , Comunicação Celular/genética , Interleucinas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Neoplasias da Mama/patologia , Linhagem da Célula/genética , Feminino , Humanos , Metástase Neoplásica
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