RESUMEN
Iron is a necessary trace element in the human body, and it participates in many physiological processes. Disorders of iron metabolism can cause lesions in many tissues and organs, including bone. Recently, iron has gained attention as an independent factor influencing bone metabolism disorders, especially the involvement of iron overload in osteoporosis. The aim of this review was to summarize the findings from clinical and animal model research regarding the involvement of iron in bone metabolism disorders and to elucidate the mechanisms behind iron overload and osteoporosis. Lastly, we aimed to describe the association between bone loss and iron overload. We believe that a reduction in iron accumulation can be used as an alternative treatment to assist in the treatment of osteoporosis, to improve bone mass, and to improve the quality of life of patients.
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Sobrecarga de Hierro , Osteoporosis , Animales , Humanos , Hierro/metabolismo , Calidad de Vida , Sobrecarga de Hierro/complicaciones , Huesos/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Osteoporosis/metabolismoRESUMEN
BACKGROUND: Brucellosis, developing complications including arthritis, spondylitis, sacroiliitis, and osteomyelitis, is one of the most common zoonotic diseases in the current world which causes economic losses to the livestock industry and is a great public health concern. Brucella melitensis are the main pathogen of brucellosis epidemics in China, most of which are located in northern China. However, there is limited knowledge about the epidemiology of osteoarthritis-associated brucellosis. This study was aimed to reveal the prevalence of osteoarthritis-associated brucellosis in Inner Mongolia and also to investigate the molecular characteristics of B. melitensis isolates. METHODS AND RESULTS: In 2018, the osteoarthritis symptoms of brucellosis in the Brucellosis department of a hospital in Inner Mongolia were investigated. Twenty osteoarthritis-associated B. melitensis strains, isolated from the inpatients in Inner Mongolia during 2013-2017, were subjected to whole genome sequencing. The multilocus sequence type (MLST) and core genome SNP (cgSNP) analysis were conducted to detect molecular epidemiological characteristics. The incidence of brucellosis osteoarthritis symptoms in males (85/120, 70.8%) was significantly higher than that in females (35/120, 29.2%), and the age of patients was concentrated between 41 and 60 years old. In silico analyses indicated ST8 was the prevalent sequence type and the transmission of osteoarthritis-associated B. melitensis among different geographical areas. All strains carry virulence genes, including cgs, lpsA, manCoAg, pgm, pmm, virB4, wbdA and wboA. CONCLUSION: Our study showed the close epidemiologically connection of osteoarthritis-associated B. melitensis strains in northern China. And ST8 was the prevalent sequence type which need our attention.
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Brucella melitensis , Brucelosis , Osteoartritis , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Brucella melitensis/genética , Tipificación de Secuencias Multilocus , Genotipo , Brucelosis/epidemiología , China/epidemiología , Osteoartritis/epidemiologíaRESUMEN
The pathogenesis of postmenopausal osteoporosis (PMOP) is mainly determined by the adhesion of osteoclasts to the bone matrix and the involvement of various molecules in bone resorption. The dual regulation strategy of the physical barriers of bone matrix and intracellular gene regulation generated by advanced biomaterials is a decent alternative for the treatment of PMOP. Herein, for the first time, it is identified that hsa-miR-378i/mmu-miR-378a-3p are closely associated with PMOP. Then, an osteophilic and dual-regulated alendronate-gene lipoplex (antagomir@Aln-Lipo), composed of medicative alendronate-functionalized liposomal vehicle and encapsulated specific microRNAs is engineered, for bone-targeting delivery of genes to achieve combined mitigation of bone loss. Alendronate targets hydroxyapatite in the bone matrix and occupies the adhesion site of osteoclasts, thus providing the "physical barriers". Antagomir is coupled precisely to specific endogenous microRNAs, thus providing the "genetic signals". These functionalized lipoplexes exhibited long-term stability and good transfection efficiency. It is proven that antagomir@Aln-Lipo could synergistically regulate osteoclastogenesis and bone resorption in vitro and in vivo. Furthermore, intravenous injection of antagomir@Aln-Lipo efficiently reverses bone loss through a dual mechanism driven by alendronate and antagomir-378a-3p. In conclusion, the osteophilic and dual-regulated antagomir@Aln-Lipo offers a brand-new bifunctional strategy for the precise treatment of PMOP.
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Resorción Ósea , MicroARNs , Humanos , Alendronato , Antagomirs , Huesos/patología , MicroARNs/genéticaRESUMEN
BACKGROUND: Fasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question. RESULTS: We used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability. CONCLUSION: STIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases.
RESUMEN
Formation of osteoclasts is known to be closely associated with osteoporosis progression. LOX is a key enzyme that catalyzes the synthesis of collagen, which is the new mediator in osteoclast formation. However, the effect of LOXG473A on of osteoclast formation needs to be explored. Thereby, we sought to explore the effect of LOXG473A on formation of osteoclasts and its underlying mechanism. To investigate the function of LOXG473A in osteoclast formation, Raw264.7 cells were stably transfected with LOX-WT or LOX-MUT (LOXG473A). Real-time PCR and western blotting were used to detect the relative levels of osteoclast formation related genes and proteins. TRAP staining and immunofluorescence staining were used to test the ability of Raw264.7 cells to form osteoclasts and the ability of cells to form rings, respectively. Bone erosion assay was used to test bone resorptive activity. The data indicated that LOXG473A significantly enhanced the ability of osteoclasts forming, ring-forming and bone resorpting in Raw264.7 cells. Mechanically, LOXG473A upregulated the expressions of NFATC1, ACP5, CTSK, IL-6, and the proportion of p-JAK2/JAK2 and p-STAT3/STAT3, thereby promoting the formation of osteoclasts. In conclusion, we have verified that LOXG473A induces the proliferation of osteoclasts in Raw264.7 cells via IL-6/JAK2/STAT3 signaling, suggesting a novel strategy for studying osteoporosis.
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Proteínas de la Matriz Extracelular/metabolismo , Interleucina-6/metabolismo , Janus Quinasa 2/metabolismo , Osteoclastos/metabolismo , Proteína-Lisina 6-Oxidasa/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/fisiología , Animales , Resorción Ósea/metabolismo , Diferenciación Celular/fisiología , Línea Celular , Ratones , Osteoclastos/fisiología , Osteogénesis/fisiología , Células RAW 264.7RESUMEN
Deficient deposition of X-rays and strong capacity of repairing damage DNA of cancer cells limit the effect of radiation therapy (RT). Herein, we synthesize CsLu2F7 nanoparticles with lactic acid (LA) ligands (CsLu2F7-LA) to overcome these limitations. The high-Z atoms of Lu and Cs can deposit more X-rays for generating enhanced hydroxyl radicals (·OH). Meanwhile, the LA ligand will guide CsLu2F7-LA to target monocarboxylic acid transporter (MCT) and impede the transportation of free LA, leading to decreased glycolysis and DNA damage repair. Consequently, the curative effect of RT will be enhanced and the strategy of LA accumulation induced radiosensitization is proved by in vivo and in vitro experiments, which will bring prospects for enhanced RT with nanomedicine.
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Ácido Láctico , Nanopartículas , Glucólisis , Reparación del ADN , Rayos XRESUMEN
Postmenopausal osteoporosis (PMOP) is mainly caused by multiple factors. Recent studies have suggested that iron accumulation (IA) was closely related to PMOP. However, the detailed molecular mechanisms have not been well demonstrated. We constructed the IA mouse model by intraperitoneal injections of ferric ammonium citrate (FAC) and cell model by culturing with the medium containing FAC. Osteoporosis was confirmed in mouse bone tissues using H&E staining, and the level of serum ferritin, alkaline phosphatase (ALP), procollagen-1 N-terminal peptide (P1NP), and osteocalcin in mice was examined by ELISA. The expressions of XIST and miR-758-3p were detected by qRT-PCR. Cell proliferation and apoptosis were measured by CCK-8, TUNEL, and flow cytometry. The expression levels of apoptotic-related proteins were evaluated by western blot. Dual luciferase reporter assay was used to examine the molecular interaction. The expressions of ALP, P1NP, and osteocalcin, and the H&E staining of bone tissues in mice were analyzed to confirm the biological function of XIST and miR-758-3p in vivo. XIST was up-regulated while miR-758-3p was down-regulated in IA mouse and cell models. XIST knockdown significantly reduced FAC-induced osteoblast apoptosis, which was mimicked by transfection with miR-758-3p mimics. XIST acted as a sponge of miR-758-3p, which targeted caspase 3. IA led to the high expression of XIST and promoted osteoblast apoptosis through miR-758-3p/caspase 3. Transfection with shXIST or miR-758-3p mimics alleviated IA-induced mouse osteoporosis. IA regulated osteoblast apoptosis through XIST/miR-758-3p/caspase 3 axis, which might provide alternative targets for the treatment of osteoporosis.
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Caspasa 3/metabolismo , Regulación de la Expresión Génica , Hierro/metabolismo , MicroARNs/genética , Osteoblastos/patología , Osteoporosis/patología , ARN Largo no Codificante/genética , Animales , Apoptosis , Caspasa 3/genética , Movimiento Celular , Proliferación Celular , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoblastos/metabolismo , Osteoporosis/etiología , Osteoporosis/metabolismoRESUMEN
BACKGROUND: Senile osteoporosis with age-related bone loss is diagnosed depending on radiographic changes of bone and bone mineral density (BMD) measurement. However, radiographic alterations are usually signs of medium-late stage osteoporosis. Therefore, biomarkers have been proposed as indicators of bone loss. In the current study, Galectin-1 (Gal-1) showed age-related decline in mice serum. The role of Gal-1 in osteoporosis has not been investigated so far. Hence, the current study illustrated the relationship of serum Gal-1 level with bone loss. METHODS: We employed 6- and 18-month-old mice to establish an animal model of age-related trabecular bone loss, whose bone density and microstructure were investigated by micro-CT. ELISA was used to measure the levels of Gal-1 in serum. The correlation analysis was performed to illustrate the relationship between serum Gal-1 levels and trabecular bone loss. In addition, immunohistochemistry was used to investigate the abundance of Gal-1 in bone marrow of mice. ELISA and western blot were performed to measure the secretion ability and protein expression of Gal-1 in bone marrow stromal cells (BMSC), hematopoietic stem cells (HSC) and myeloid progenitor (MP) respectively. Flow cytometry was used to measure BMSC number in bone marrow. Finally, male volunteers with age-related BMD decrease were recruited and the relationship between serum Gal-1 and BMD was analyzed. RESULTS: Gal-1 showed age-related decline in mice serum. Serum Gal-1 was positively associated with BV/TV of femur, tibia and L1 vertebrae in mice. BMSC secreted more Gal-1 compared with HSC and MP. BMSC number in bone marrow was significantly lower in aged mice compared with young mice. Significant attenuation of Gal-1 protein expression was observed in BMSC and HSC from aged mice compared with young mice. Further, we found a decline in serum Gal-1 levels in men with age-related BMD decrease. There was positive correlation between BMD and serum Gal-1 levels in these men. CONCLUSIONS: Age-related trabecular bone loss is associated with a decline in serum Gal-1 level in mice and men. Our study suggested Gal-1 had great potential to be a biomarker for discovering BMSC senescence, diagnosing early osteoporosis and monitoring trabecular bone loss.
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Galectina 1 , Osteoporosis , Animales , Densidad Ósea , Hueso Esponjoso/diagnóstico por imagen , Masculino , Osteoporosis/diagnóstico por imagen , TibiaRESUMEN
BACKGROUND: The present study aimed to investigate the effect of cnidium lactone on ovariectomy (OVX)-induced bone loss and determine whether it exerts its effects by mediating the estrogen receptor-α (ERα)/bone morphogenetic protein-2 (BMP-2)/Smad signaling pathways. METHODS: Fifty-five female rats were randomly assigned to the following treatment groups: the OVX group, the sham-operated (sham) group, and groups treated with cnidium lactone at different doses (10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day). Treatments were administered for 60 days. Search Tool for Interacting Chemicals (STITCH; http://stitch.embl.de) was used to identify the interaction between cnidium lactone and target proteins. Bone mineral density (BMD), mechanical strength, serum osteoblastic and osteoclastic markers, and hematoxylin and eosin (HE) staining of the distal femur were evaluated. Moreover, western blot analyses were also performed to evaluate the effect of cnidium lactone on the ERα/BMP-2/Smad signaling pathway. RESULTS: Cnidium lactone treatment was associated with an increase in the BMD of the distal femur compared to that of the OVX group. Moreover, cnidium lactone significantly increased biomechanical properties in a dose-dependent manner compared to those of the OVX group (p < 0.05). Treatment with cnidium lactone significantly enhanced the BMP-2/Smad signaling pathway by up-regulating the expression of ERα, BMP-2, p-Smad1 and p-Smad4. Cnidium lactone treatment improved the microstructure of trabecular bone in the distal femurs of OVX rats, as shown by HE staining. CONCLUSIONS: Cnidium lactone exerts potent antiosteoporotic activity in ovariectomized mice, and the underlying molecular mechanism may be related to the ERα/BMP-2/Smad signaling pathways.
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Proteína Morfogenética Ósea 2/metabolismo , Estrógenos/metabolismo , Lactonas/farmacología , Osteogénesis/efectos de los fármacos , Transducción de Señal , Proteínas Smad/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Cnidium/química , Femenino , Ovariectomía , Ratas , Ratas Sprague-Dawley , Urea/sangreRESUMEN
PURPOSE: To assess the clinical efficacy of converting partial articular supraspinatus tendon avulsion (PASTA) lesions to full-thickness tears through a small local incision of the bursal-side supraspinatus tendon followed by repair. METHODS: We retrospectively analyzed 41 patients with Ellman grade 3 PASTA lesions and an average age of (54.7 ± 11.4) years from March 2013 to July 2017. Patients without regular conservative treatment and concomitant with other shoulder pathologies or previous shoulder surgery were excluded from the study. The tears were confirmed via arthroscopy, and a polydioxanone suture was placed to indicate the position of each tear. A small incision of approximately 6 mm was made using a plasma scalpel on the bursal-side supraspinatus tendon around the positioned suture to convert the partial tear into a full-thickness tear. The torn rotator cuff was sutured through the full thickness using a suture passer after inserting a 4.5-mm double-loaded suture anchor. Data were analyzed using a paired Student's t-test with statistical significance defined as p <0.05. RESULTS: At the final follow-up of 2 years, the pain-free shoulder joint range of motion and visual analog scale score were significantly improved compared to those before surgery (p < 0.001). The postoperative American Shoulder and Elbow Surgeons shoulder score was (90.6 ± 6.2), which was significantly higher than the preoperative score of (47.9 ± 8.3) (p < 0.001). The University of California at Los Angeles shoulder rating scale score increased from (14.7 ± 4.1) prior to surgery to (32.6 ± 3.4) points after surgery (p < 0.001). No patient had joint stiffness. CONCLUSION: This modified tear completion repair, by conversion to full-thickness tears through a small incision, has less damage to the supraspinatus tendon on the side of the bursa compared to traditional tear completion repair in the treatment of PASTA lesions. This surgical method is a simple and effective treatment that can effectively alleviate pain and improve shoulder joint function.
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Artroscopía/métodos , Manguito de los Rotadores , Técnicas de Sutura , Traumatismos de los Tendones/cirugía , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Estudios Retrospectivos , Traumatismos de los Tendones/fisiopatología , Resultado del TratamientoRESUMEN
Sclerostin (SOST), a glycoprotein predominantly secreted by bone tissue osteocytes, is an important regulator of bone formation, and loss of SOST results in Van Buchem disease. DNA methylation regulates SOST expression in human osteocytes, although the detailed underlying mechanisms remain unknown. In this study, we compared 12 patients with bone fractures and postmenopausal osteoporosis with eight patients without postmenopausal osteoporosis to understand the mechanisms via which SOST methylation affects osteoporosis. Serum and bone SOST expression was reduced in patients with osteoporosis. Bisulfite sequencing polymerase chain reaction revealed that the methylation rate was higher in patients with osteoporosis. We identified osterix (SP7), Runt-related transcription factor 2 (RUNX2), and estrogen receptor α (ERα) as candidate transcription factors activating SOST expression. Increased SOST methylation impaired the transactivation function of SP7, RUNX2, and ERα in MG-63 cells. AzadC treatment and SOST overexpression in MG-63 cells altered cell proliferation and apoptosis. Chromatin immunoprecipitation showed that higher methylation was associated with reduced SP7, RUNX2, and ERα binding to the SOST promoter in patients with osteoporosis. Our studies provide new insight into the role of SOST methylation in osteoporosis.
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Proteínas Morfogenéticas Óseas/metabolismo , Huesos/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Receptor alfa de Estrógeno/metabolismo , Osteoporosis Posmenopáusica/metabolismo , Factor de Transcripción Sp7/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Apoptosis/efectos de los fármacos , Proteínas Morfogenéticas Óseas/genética , Huesos/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Decitabina/farmacología , Marcadores Genéticos/genética , Humanos , Metilación/efectos de los fármacos , Osteoporosis Posmenopáusica/patologíaRESUMEN
BACKGROUND Angiopoietin-like proteins (ANGPTL) are a family of secretory glycoproteins that are involved in many pathophysiological processes. ANGPTL7 is a newly-discovered member of the ANGPTL family and plays a role in corneal morphogenesis, angiogenesis, glaucoma, and cancer. To date, whether ANGPTL7 is involved in osteoporosis is unknown. Therefore, to discover the effects of ANGPTL7 on osteoporosis, we explored the expression of ANGPTL7 in preosteoblasts and assessed the mechanism underlying its effects on proliferation and differentiation abilities of preosteoblasts. MATERIAL AND METHODS Mouse MC3T3-E1 cells were cultured in osteogenic medium for osteogenic differentiation. The expression levels of ANGPTL7 were detected by RT-qPCR and Western blot assays. Moreover, the overexpressed plasmid of ANGPTL7 pMSCV-ANGPTL7 was transfected into MC3T3-E1 cells. CCK-8 was used to evaluate cell proliferation. ALP activity detection and alizarin red staining were performed to measure the effect of ANGPTL7 on osteogenic differentiation. The expression levels bone morphogenetic proteins (BMPs) and osteogenic markers ALP, runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and collagen I (Col I) were analyzed by Western blot. RESULTS When MC3T3-E1 cells were exposed to osteogenic medium, there was a significant increase in ANGPTL7, and overexpression of ANGPTL7 markedly promoted cell proliferation, ALP activity, and mineralization. Moreover, ANGPTL7 upregulated the levels of BMPs, especially BMP2/7, and the osteogenic markers ALP, Runx2, OCN, and Col I. CONCLUSIONS The results suggest that by regulating the expression of BMPs, ANGPTL7 directly promotes proliferation, differentiation, and mineralization of osteoblasts.
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Proteínas Similares a la Angiopoyetina/metabolismo , Células 3T3 , Proteína 7 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina/biosíntesis , Angiopoyetinas/metabolismo , Animales , Biomarcadores/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Diferenciación Celular/fisiología , Línea Celular , Proliferación Celular/fisiología , Colágeno Tipo I/metabolismo , Ratones , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteogénesis/fisiología , Osteoporosis/metabolismoRESUMEN
Osteoblasts and osteoclasts are responsible for the formation and resorption of bone, respectively. An imbalance between these two processes results in a disease called osteoporosis, in which a decreased level of bone strength increases the risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of 18-25 nucleotides that have been previously shown to control bone metabolism by regulating osteoblast and osteoclast differentiation. In this study, we detected the expression pattern of 10 miRNAs in serum samples from patients with osteoporosis, and identified the altered expression of 6 miRNAs by comparison with patients without osteoporosis. We selected miR-144-3p for further investigation, and showed that it regulates osteoclastogenesis by targeting RANK, and that it is conserved amongst vertebrates. Disrupted expression of miR-144-3p in CD14+ peripheral blood mononuclear cells changed TRAP activity and the osteoclast-specific genes TRAP, cathepsin K (CTSK), and NFATC. TRAP staining, CCK-8, and flow cytometry analyses revealed that miR-144-3p also affects osteoclast formation, proliferation, and apoptosis. Together, these results indicate that miR-144-3p critically mediates bone homeostasis, and thus, represents a promising novel therapeutic candidate for the treatment of this disease.
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Huesos/metabolismo , Regulación de la Expresión Génica , Leucocitos Mononucleares/metabolismo , MicroARNs/biosíntesis , Osteoporosis/sangre , Receptor Activador del Factor Nuclear kappa-B/sangre , Apoptosis , Huesos/patología , Proliferación Celular , Femenino , Humanos , Leucocitos Mononucleares/patología , Masculino , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis/patologíaRESUMEN
BACKGROUND/AIMS: Bone marrow mesenchymal stem cells (BMSCs) play an essential role in osteoporosis. However, the molecular mechanisms and the involvement of glutamine metabolism in osteogenic BMSCs differentiation and osteoporosis remain largely unclear. In this study, we investigated the role of Golgi membrane protein 1 (GOLM1) and glutamine metabolism in BMSCs differentiation and osteoporosis. METHODS: Osteogenic differentiation-inducing media (Odi) was used to induce the osteogenic differentiation of BMSCs. The mRNA expression of GOLM1, ALP, Runx2, Osx, BSP and OCN was determined by qRT-PCR assay. Western blot assay was used to analyze GOLM1, p-mTOR, mTOR, p-S6 and S6 abundance in GOLM1 silencing and over-expressed BMSCs. Glutamine uptake, intracellular glutamine, glutamate and α-KG level was detected using indicated Kits. GOLM1 antibody, glutamine metabolism inhibitors EGCG and BPTES were used to treat ovariectomy (OVX)-induced osteoporosis. Bone mineral density and bone volume relative to tissue volume (%) were analyzed by micro-CT. Serum was collected from osteoporosis patients and healthy participants and subjected to GOLM1 determination using ELISA Kit. RESULTS: GOLM1 expression and glutamine metabolism were suppressed by Odi. GOLM1 blockage or inhibition of glutamine metabolism promoted the osteogenic differentiation of BMSCs induced by Odi. GOLM1 activated glutamine metabolism depending on the mTOR signaling pathway. In vivo, GOLM1 antibody or combination of glutamine inhibitor EGCG and BPTES rescued the osteoporosis in an OVX-operated mouse model. Serum GOLM1 level was increased in the patients of osteoporosis compared with healthy people. CONCLUSION: GOLM1 stimulates glutamine metabolism to suppress the osteogenic differentiation of BMSCs and to promote osteoporosis. Therefore, GOLM1 activation of glutamine metabolism is a potential target for osteoporosis.
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Diferenciación Celular , Glutamina/metabolismo , Proteínas de la Membrana/metabolismo , Animales , Células de la Médula Ósea/citología , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Femenino , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Osteogénesis , Osteoporosis/metabolismo , Osteoporosis/patología , Ovariectomía , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Many studies have reported associations between estrogen receptor (ER) gene polymorphisms and postmenopausal osteoporosis (PMOP) risk and bone mineral density (BMD), but the results are controversial. The aim of the present meta-analysis is to verify the association between ERα and ERß gene polymorphisms and osteoporosis susceptibility and BMD in postmenopausal women. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library and China WeiPu Library were searched. OR and WMD with 95% CI were calculated to assess the association. RESULTS: Overall, no significant association was observed between ERα XbaI, ERα PvuII and PMOP susceptibility in either overall, Caucasian or Asian populations. ERα G2014A was significantly associated with a decreased risk of PMOP in Caucasian populations. There was a significant association between ERß RsaI and PMOP risk in both overall and Asian populations. Caucasian PMOP women with ERα XbaI XX and Xx genotypes had a higher LS Z value than women with xx genotype. ERα XbaI XX genotype was associated with increased FN BMD in overall and Caucasian populations, an increased FN Z value in Asians, and a decreased FN Z value in Caucasians. There was also a significant association between ERα XbaI Xx genotype and an increased FN Z value in either Asians or Caucasians. ERα PvuII PP genotype was associated with a low LS Z value in Caucasians and a low FN BMD and Z value in Asians. Pp genotype in PMOP women was significantly correlated with low LS BMD in overall populations, a low FN Z value in either overall, Caucasian or Asian populations. CONCLUSION: Each ERα and ERß gene polymorphism might have different impact on PMOP risk and BMD in various ethnicities.
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Densidad Ósea , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Predisposición Genética a la Enfermedad , Osteoporosis Posmenopáusica/genética , Polimorfismo Genético , Femenino , Genotipo , Humanos , Osteoporosis Posmenopáusica/patologíaRESUMEN
BACKGROUND MicroRNAs (miRNAs) play a crucial role in regulating diverse biological processes, including drug resistance. We investigated the potential roles of the miR-29 family in methotrexate (MTX) resistance in osteosarcoma. MATERIAL AND METHODS Two MTX-resistant osteosarcoma cell lines, MG-63/MTX and U2OS/MTX, were generated by continuous exposure to stepwise increasing concentrations of MTX. miR-29abc, COL3A1, and MCL1 mRNA expression levels were determined using quantitative real-time PCR (qRT-PCR). Protein expression levels of COL3A1 and MCL1 were detected by Western blot. Cell viability, IC50 value, and cell apoptosis were assessed by CCK-8 assay and flow cytometry, respectively. The target relationship between the miR-29 family and COL3A1 or MCL1 was confirmed by luciferase reporter assay. RESULTS miR-29a, miR-29b, and miR-29c were significantly downregulated in MG-63/MTX and U2OS/MTX cells and in chemotherapy poor-response osteosarcoma tissues. Overexpression of the miR-29 family sensitized MG-63/MTX and U2OS/MTX cells to MTX and obviously promoted cell apoptosis compared with negative control. COL3A1 and MCL1 were identified to be target genes of the miR-29 family, and transfection with miR-29abc mimics in MG-63/MTX and U2OS/MTX cells decreased COL3A1 and MCL1 mRNA and protein expression. Meanwhile, overexpression of COL3A1 and MCL1 partly neutralized the effects of the miR-29 family on MTX resistance and cell apoptosis. CONCLUSIONS Taken together, our findings suggested a tumor-suppressor role of the miR-29 family in control of MTX resistance and cell apoptosis through regulating COL3A1 or MCL1. Targeting the miR-29 family might provide new strategies to overcome the high-dosage MTX-induced cytotoxicity in osteosarcoma treatment.
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Neoplasias Óseas/tratamiento farmacológico , Colágeno Tipo III/metabolismo , Metotrexato/farmacología , MicroARNs/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Osteosarcoma/tratamiento farmacológico , Apoptosis/fisiología , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular/fisiología , Supervivencia Celular/fisiología , Colágeno Tipo III/genética , Regulación hacia Abajo , Resistencia a Antineoplásicos , Humanos , Metotrexato/metabolismo , MicroARNs/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Regulación hacia ArribaRESUMEN
BACKGROUND: The aim of this study was to determine the functional and radiological outcomes of arthroscopic treatment of anterior ankle impingement (AAI) in patients with chronic lateral ankle instability (CAI). METHODS: All patients with CAI between June 2012 and May 2015 were invited to participate in this investigation. All of them accepted open modified Broström repair of lateral ankle ligaments and were divided into two groups: AAI group (with anterior ankle impingement) and pure CAI group (without anterior ankle impingement). All of them were followed up using American Orthopaedic Foot and Ankle Society Score (AOFAS), Karlsson Ankle Functional Score and Tegner activity score. Ankle dorsiflexion was also examined. X-ray examination was applied to investigate anterior tibiotalar osteophytes. RESULTS: Finally, a total of 60 patients were followed up at a mean of 37 ± 10 months, including 22 patients in the AAI group and 38 patients in the pure CAI group. Preoperatively, the AAI group had significant lower AOFAS score (62.9 ± 11.7 vs 72.9 ± 11.1; p = 0.002) and Tegner activity score (1.5 ± 0.8 vs 2.1 ± 1.0; p = 0.04) respectively when compared with the pure CAI group. The ankle dorsiflexion of the AAI group (13 ± 2.1) was also significantly lower than that of the pure CAI group (26.2 ± 2.1) (p = 0.001). However, there was no significant difference in the AOFAS score or the Karlsson score or the Tegner score or the Ankle dorsiflexion between the two groups postoperatively. The postoperative X-ray images demonstrated complete osteophyte resection in all patients, and no recurrence of osteophyte. CONCLUSION: The functional outcome scores and dorsiflexion had significantly improved postoperatively. Combined treatment of chronic ankle instability and anterior ankle impingement produced satisfactory surgical outcomes in patients with CAI accompanied by anterior ankle impingement symptom.
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Artroscopía/métodos , Desbridamiento/métodos , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/cirugía , Ligamentos Laterales del Tobillo/diagnóstico por imagen , Ligamentos Laterales del Tobillo/cirugía , Adulto , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/cirugía , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to investigate clinical outcomes of fifth metacarpal neck fractures using antegrade single elastic nail and to explore ideal puncture point to avoid iatrogenic ulnar nerve injury. METHODS: A single elastic nail with suitable diameter was used in 27 cases of fifth metacarpal neck fractures with dorsal angulation over 45°. An initial entry point was perforated at the ulnar-dorsal base of the metacarpal. The nail was inserted in an antegrade approach. The nail was usually removed at about 5 weeks postoperatively. RESULTS: At final follow up, all fractures proceeded to bony union. The mean total passive motion was 285° and the mean total active motion (TAM) was 270°. The mean angulation decreased from 50.2 ± 6.3° preoperatively to 7.4 ± 2.3° postoperatively (p < 0.001). The mean DASH-Score was 2.1 ± 3.6 points after surgery. Two cases of skin irritation and one case of the dorsal cutaneous branch of the ulnar nerve (DCBUN) injury were observed. Superficial wound infections were not observed. CONCLUSIONS: Collectively, antegrade single elastic intramedullary nailing was a minimally invasive and reliable fixation technique for fifth metacarpal neck fractures with dorsal angulation over 45°. Appropriate puncture position helped to reduce nerve damage.
Asunto(s)
Fijación Intramedular de Fracturas/métodos , Fracturas Óseas/cirugía , Huesos del Metacarpo/lesiones , Huesos del Metacarpo/cirugía , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Fracturas Óseas/diagnóstico por imagen , Humanos , Masculino , Huesos del Metacarpo/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Iron overload, as a risk factor for osteoporosis, can result in the up-regulation of Hepcidin, and Hepcidin knockout mice display defects in their bone microarchitecture. However, the molecular and genetic mechanisms underlying Hepcidin deficiency-derived bone loss remain unclear. Here, we show that hepcidin knockdown in zebrafish using morpholinos leads to iron overload. Furthermore, a mineralization delay is observed in osteoblast cells in hepcidin morphants, and these defects could be partially restored with microinjection of hepcidin mRNA. Quantitative real-time PCR analyses revealed the osteoblast-specific genes alp, runx2a, runx2b, and sp7 in morphants are down-regulated. Furthermore, we confirmed qRT-PCR results by in situ hybridization and found down-regulated genes related to osteoblast function in hepcidin morphants. Most importantly, we revealed that hepcidin was capable of removing whole-body iron which facilitated larval recovery from the reductions in bone formation and osteogenesis induced by iron overload.
Asunto(s)
Técnicas de Silenciamiento del Gen , Hepcidinas/genética , Sobrecarga de Hierro/genética , Osteogénesis , Proteínas de Pez Cebra/metabolismo , Pez Cebra/fisiología , Secuencia de Aminoácidos , Animales , Huesos/metabolismo , Huesos/patología , Regulación hacia Abajo , Hepcidinas/química , Hepcidinas/metabolismo , Hierro/metabolismo , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/patología , Morfolinos/genética , Osteoblastos/metabolismo , Osteoblastos/patología , Filogenia , ARN Mensajero/genética , Pez Cebra/genética , Proteínas de Pez Cebra/química , Proteínas de Pez Cebra/genéticaRESUMEN
Iron is one of the essential elements of life. Iron metabolism is related to bone metabolism. Previous studies have confirmed that iron overload is a risk factor for osteoporosis. But the correlation between iron deficiency and bone metabolism remains unclear. Ferroportin 1 is identified as a cellular iron exporter and required for normal iron cycling. In zebrafish, the mutant of ferroportin 1 gene (fpn1), weh(tp85c) exhibited the defective iron transport, leading to developing severe hypochromic anemia. We used weh(tp85c) as a model for investigating iron deficiency and bone metabolism. In this study, we examined the morphology of the developing cartilage and vertebrae of the Weh(tp85) compared to the wild type siblings by staining the larvae with alcian blue for cartilage and alizarin red for the bone. In addition, we evaluated the expression patterns of the marker genes of bone development and cell signaling in bone formation. Our results showed that weh(tp85c) mutant larvae exhibited the defects in bone formation, revealing by decreases in the number of calcified vertebrae along with decreased expression of osteoblast novel genes: alpl, runx2a and col1a1a and BMPs signaling genes in osteoblast differentiation: bmp2a and bmp2b. Our data suggest that iron deficiency anemia affects bone formation, potentially through the BMPs signaling pathway in zebrafish.