RESUMEN
Ganoderic Acid A (GAA) has demonstrated beneficial effects in anti-inflammatory and anti-oxidative stress studies. However, it remains unknown whether GAA exerts positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of GAA on bone loss in LPS-treated rats. The study assesses changes in the viability and osteogenic potential of MC3T3-E1 cells, as well as osteoclast differentiation in RAW264.7 cells in the presence of LPS using CCK-8, ALP staining, AR staining, and Tartrate-resistant acid phosphatase (TRAP) staining. In vitro experiments indicate that LPS-induced inhibition of osteoclasts (OC) and Superoxide Dismutase 2 (SOD2) correlates with heightened levels of inflammation and oxidative stress. Furthermore, GAA has displayed the ability to alleviate oxidative stress and inflammation, enhance osteogenic differentiation, and suppress osteoclast differentiation. Animal experiment also proves that GAA notably upregulates SOD2 expression and downregulates TNF-α expression, leading to the restoration of impaired bone metabolism, improved bone strength, and increased bone mineral density. The collective experimental findings strongly suggest that GAA can enhance osteogenic activity in the presence of LPS by reducing inflammation and oxidative stress, hindering osteoclast differentiation, and mitigating bone loss in LPS-treated rat models.
Asunto(s)
Diferenciación Celular , Ácidos Heptanoicos , Inflamación , Lanosterol , Lipopolisacáridos , Osteoclastos , Osteogénesis , Estrés Oxidativo , Ratas Sprague-Dawley , Superóxido Dismutasa , Animales , Lipopolisacáridos/farmacología , Estrés Oxidativo/efectos de los fármacos , Masculino , Ratones , Ratas , Células RAW 264.7 , Superóxido Dismutasa/metabolismo , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Diferenciación Celular/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Lanosterol/análogos & derivados , Lanosterol/farmacología , Lanosterol/uso terapéutico , Ácidos Heptanoicos/farmacología , Ácidos Heptanoicos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Resorción Ósea/prevención & control , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismoRESUMEN
The accumulating evidence has made it clear that iron overload is a crucial mechanism in bone loss. Protocatechualdehyde (PCA) has also been used to prevent osteoporosis in recent years. Whether PCA can reverse the harmful effects of iron overload on bone mass in aged rats is still unknown. Therefore, this study aimed to assess the role of PCA in iron overload-induced bone loss in senile rats. In the aged rat model, we observed that iron overload affects bone metabolism and bone remodeling, manifested by bone loss and decreased bone mineral density. The administration of PCA effectively mitigated the detrimental effects caused by iron overload, and concomitant reduction in MDA serum levels and elevation of SOD were noted. In addition, PCA-treated rats were observed to have significantly increased bone mass and elevated expression of SIRT3ï¼BMP2ï¼SOD2 and reduced expression of TNF-α in bone tissue. We also observed that PCA was able to reduce oxidative stress and inflammation and restore the imbalance in bone metabolism. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclasts differentiation, PCA intervention could significantly recover the restriction of osteogenic differentiation and up-regulation of osteoclast differentiation treated by iron overload. Further, by detecting changes in ROS, SOD, MDA, expression of SIRT3 and mitochondrial membrane potentials, we confirm that the damage caused to cells by iron overload is associated with decreased SIRT3 activity, and that 3-TYP have similar effects on oxidative stress caused by FAC. In conclusion, PCA can resist iron overload-induced bone damage by improving SIRT3 activity, anti-inflammatory and anti-oxidative stress.
RESUMEN
OBJECTIVES: The study aimed to assess the role of Astaxanthin (ATX) in palmitic acid(PA) -induced bone loss in Ovariectomized(OVX) rats. METHODS: In the OVX rat model, we observed that PA affects bone metabolism and accelerates bone loss. Additionally, treatment with ATX was able to suppress the deleterious effects of PA and a simultaneous decrease in serum MDA levels and an increase in SOD was observed. RESULTS: In addition, rats treated with ATX were observed to have significantly increased bone mass and elevated activity of SIRT1 and SOD2 in bone tissue. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclast differentiation, the ATX intervention was able to significantly restore the restriction of osteogenic differentiation and the up-regulation of osteoclast differentiation with PA therapy. Furthermore, we confirm that PA damage to cells is caused by increased oxidative stress, and that ATX can target and modulate the activity of SIRT1 to regulate the levels of oxidative stress in cells. CONCLUSION: Summarizing, ATX may inhibit PA-induced bone loss through its antioxidant properties via the SIRT1 signaling pathway.
Asunto(s)
Osteoporosis , Ratas , Animales , Osteoporosis/tratamiento farmacológico , Osteoporosis/prevención & control , Osteogénesis , Ácido Palmítico/toxicidad , Sirtuina 1 , Diferenciación Celular , Estrés Oxidativo , XantófilasRESUMEN
Recently, more and more studies have revealed that iron overload can lead to osteoporosis by inducing oxidative stress. Niacin (NAN), also known as nicotinate or vitamin B3, has been confirmed to possess potent antioxidative effects. In addition, very little is currently known about the protective effects of NAN on iron overload in osteoporotic bone tissue. Therefore, we aimed to evaluate the protective effect of niacin on iron overload-induced bone injury and to investigate the effect and underlying mechanisms of the niacin and iron overload on intracellular antioxidant properties. When MC3T3-E1 and RAW264.7 cells were cultured in the presence of ammonium ferric citrate(FAC), NAN therapy could increase the matrix mineralization and promote expression of osteogenic markers in MC3T3-E1, inhibit osteoclastic differentiation of RAW264.7 cells, while increasing intracellular reactive oxygen species (ROS) levels and strengthening mitochondrial membrane potential (MMP). In the ovariectomized (OVX) rat model, NAN had an obvious protective effect against iron-overloaded injury. Meanwhile, superoxide dismutase 2 (SOD2), intracellular antioxidant enzymes and silent information regulator type 1 (SIRT1), were up-regulated in response to NAN exposures in MC3T3-E1. Furthermore, SIRT1 inhibitor EX527 attenuated the protective effects of NAN. Results revealed that NAN could stimulate osteogenic differentiation, inhibit osteoclastic differentiation and markedly increased antioxidant properties in cells through the induction of SIRT1. Studies suggest that niacin is a promising agent for preventing bone loss in iron overload conditions.
Asunto(s)
Sobrecarga de Hierro , Niacina , Animales , Ratas , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/tratamiento farmacológico , Niacina/farmacología , Niacina/uso terapéutico , Osteogénesis , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Sirtuina 1/metabolismoRESUMEN
OBJECTIVE: The purpose is to observe whether local administration with selenium (Se) can enhance the efficacy of calcium phosphate cement (CPC) in the treatment of osteoporotic bone defects. METHODS: Thirty ovariectomized (OVX) rats with two defects were generated and randomly allocated into the following graft study groups: (1) OVX group (n = 10), (2) CPC group (n = 10); and (3) Se-CPC group (n = 10). Then, these selenium-modified calcium phosphate cement (Se-CPC) scaffolds were implanted into the femoral epiphysis bone defect model of OVX rats for 12 weeks. Micro-CT, history, western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and to explore the possible mechanism. RESULT: Micro-CT and histological analysis evaluation showed that the Se-CPC group presented the strongest effect on bone regeneration and bone mineralization when compared with the CPC group and the OVX group. Protein expressions showed that the oxidative stress protein expressions, such as SOD2 and GPX1 of the Se-CPC group, are significantly higher than those of the OVX group and the CPC group, while Se-CPC remarkably reduced the expression of CAT. RT-qPCR analysis showed that the Se-CPC group displayed more OPG than the OVX and CPC groups (p < 0.05), while Se-CPC exhibited less RANKL than the OVX and CPC groups (p < 0.05). CONCLUSION: Our current study demonstrated that Se-CPC is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by inhibiting local oxidative stress and through OPG/RANKL signaling pathway.
Asunto(s)
Osteoporosis , Selenio , Animales , Cementos para Huesos/farmacología , Regeneración Ósea , Fosfatos de Calcio/farmacología , Osteoporosis/tratamiento farmacológico , Ratas , Selenio/farmacologíaRESUMEN
Despite advances in the pathogenesis of Tauroursodeoxycholic acid (TUDCA) on bone, the understanding of the effects and mechanisms of bone osseointegration in TUDCA-associated Hydroxyapatite (HA)-coated titanium implants remains poor. Therefore, the present work was aimed to evaluate the effect of local administration with TUDCA on HA-coated titanium implants osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: sham operation(Sham) group, OVX group and TUDCA group, and all the rats from Sham group and OVX group received HA implants and animals belonging to group TUDCA received TUDCA-HA implants until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. TUDCA increased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed systemic TUDCA showed positive effects than OVX group on bone formation in osteopenic rats, with beneficial effect on via activation OPG/RANKL pathway and BMP-2/Smad1 pathway and microarchitecture as well as by reducing protein expression of TNF-α and IFN-γ. The present study suggests that local use of TUDCA may bring benefits to the osseointegration of HA-coated titanium implants in patients with osteoporosis, and this effect may be related to the inhibition of inflammatory reaction and promotion of osteogenesis.
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Materiales Biocompatibles Revestidos/química , Durapatita/química , Oseointegración/efectos de los fármacos , Ácido Tauroquenodesoxicólico/farmacología , Titanio/química , Animales , Femenino , Ovariectomía , Prótesis e Implantes , Ratas , Ratas Sprague-Dawley , Ácido Tauroquenodesoxicólico/administración & dosificaciónAsunto(s)
Portadores de Fármacos/química , Durapatita/química , Oseointegración/efectos de los fármacos , Osteoporosis/prevención & control , Silimarina/química , Titanio/química , Animales , Regeneración Ósea , Materiales Biocompatibles Revestidos/química , Liberación de Fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Modelos Animales , Prótesis e Implantes , Ratas , Ratas Sprague-Dawley , Silimarina/administración & dosificación , Propiedades de SuperficieRESUMEN
Composite materials ß-tricalcium phosphate (ß-TCP) and poly-lactic-co-glycolic acid (PLGA) have achieved stable bone regeneration without cell transplantation in previous studies. Recent research shows that aspirin (ASP) has great potential in promoting bone regeneration. The objective of the present study was to incorporate PLGA into ß-TCP combined with a lower single-dose local administration of ASP to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, PLGA -modified ß-TCP (TP) was prepared by mixing sieved granules of ß-TCP and PLGA (50:50, v/v) for medical use, then TP with dripped 50 µg/0.1 ml and 100 µg/0.1 ml aspirin solution was implanted into the defect of OVX rats until death at 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, biomechanics and real time RT-PCR. The results of our study show that a single-dose local administration of ASP combined with the local usage of TP can increase the healing of defects in OVX rats. Single-dose local administration of aspirin can improve the transcription of genes involved in the regulation of bone formation and vascularization in the defect area, and inhibits osteoclast activity. Furthermore, treatments with a higher single-dose local administration of ASP and TP showed a stronger effect on accelerating the local bone formation than while using a lower dose of ASP. The results from our study demonstrate that the combination of a single-dose local administration of ASP and ß-TCP/PLGA had an additive effect on local bone formation in osteoporosis rats, and bone regeneration by PLGA/ß-TCP/ASP occured in a dose-dependent manner.
Asunto(s)
Aspirina/administración & dosificación , Aspirina/uso terapéutico , Regeneración Ósea , Fosfatos de Calcio/administración & dosificación , Osteoporosis/tratamiento farmacológico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/administración & dosificación , Animales , Aspirina/farmacología , Biomarcadores/metabolismo , Fenómenos Biomecánicos , Regeneración Ósea/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoporosis/diagnóstico por imagen , Ovariectomía , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Microtomografía por Rayos XRESUMEN
Recently, the use of the pharmacological agents strontium ranelate (SR), parathyroid hormone (1-34, PTH) and zoledronic acid (ZA) has come to prominence for the treatment of osteoporosis due to their ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on which one is more effective. There is still no direct comparative study on these three drugs. The aim of the present study was to investigate the effect of SR, PTH, ZA on preventing ovariectomy-induced osteoporosis in rats. After bilateral ovariectomy the rats randomly received vehicle, SR (500â¯mg/kg body weight/day, orally), PTH (20⯵g/kg/day, subcutaneously) or a single injection of ZA (0.1â¯mg/kg, i.v.) until death at 12 weeks. The distal femurs were harvested for evaluation of bone metabolism. The rats treated with ZA demonstrated the highest levels of new bone formation as assessed by microcomputed tomography (CT), biomechanical strength, histological analysis and bone metabolism. Furthermore, PTH and SR showed a stronger effect on improving trabecular bone mass at 12 weeks. The results from the present study demonstrate that systemic administration of PTH, SR and ZA could prevent bone loss, while a single dose of ZA has a better effect on preventing ovariectomy-induced osteoporosis than either PTH or SR.