RESUMO
Calcium phosphate cement (CPC) porous scaffold is widely used as a suitable bone substitute to repair bone defect, but the optimal pore size is unclear yet. The current study aimed to evaluate the effect of different pore sizes on the processing of bone formation in repairing segmental bone defect of rabbits using CPC porous scaffolds. Three kinds of CPC porous scaffolds with 5 mm diameters and 12 mm length were prepared with the same porosity but different pore sizes (Group A: 200-300 µm, Group B: 300-450 µm, Group C: 450-600 µm, respectively). Twelve millimeter segmental bone defects were created in the middle of the radius bone and filled with different kinds of CPC cylindrical scaffolds. After 4, 12, and 24 weeks, alkaline phosphatase (ALP), histological assessment, and mechanical properties evaluation were performed in all three groups. After 4 weeks, ALP activity increased in all groups but was highest in Group A with smallest pore size. The new bone formation within the scaffolds was not obvious in all groups. After 12 weeks, the new bone formation within the scaffolds was obvious in each group and highest in Group A. At 24 weeks, no significant difference in new bone formation was observed among different groups. Besides the osteoconductive effect, Group A with smallest pore size also had the best mechanical properties in vivo at 12 weeks. We demonstrate that pore size has a significant effect on the osteoconductivity and mechanical properties of calcium phosphate cement porous scaffold in vivo. Small pore size favors the bone formation in the early stage and may be more suitable for repairing segmental bone defect in vivo.
Assuntos
Cimentos Ósseos/uso terapêutico , Regeneração Óssea , Substitutos Ósseos/uso terapêutico , Fosfatos de Cálcio/uso terapêutico , Osteogênese , Fosfatase Alcalina/metabolismo , Animais , Fenômenos Biomecânicos , Cimentos Ósseos/química , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/química , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/lesões , Fosfatos de Cálcio/química , Masculino , Osteogênese/efeitos dos fármacos , Porosidade , Coelhos , Alicerces Teciduais/químicaRESUMO
Estrogen deficiency is the main reason of bone loss, leading to postmenopausal osteoporosis, and estrogen replacement therapy (ERT) has been demonstrated to protect bone loss efficiently. Notch signaling controls proliferation and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Moreover, imperfect estrogen-responsive elements (EREs) were found in the 5'-untranslated region of Notch1 and Jagged1. Thus, we examined the molecular and biological links between estrogen and the Notch signaling in postmenopausal osteoporosis in vitro. hBMSCs were obtained from healthy women and patients with postmenopausal osteoporosis. Notch signaling molecules were quantified using real-time polymerase chain reaction (real-time PCR) and Western Blot. Luciferase reporter constructs with putative EREs were transfected into hBMSCs and analyzed. hBMSCs were transduced with lentiviral vectors containing human Notch1 intracellular domain (NICD1). We also used N-[N-(3, 5-diflurophenylacetate)-l-alanyl]-(S)-phenylglycine t-butyl ester, a γ-secretase inhibitor, to suppress the Notch signaling. We found that estrogen enhanced the Notch signaling in hBMSCs by promoting the expression of Jagged1. hBMSCs cultured with estrogen resulted in the up-regulation of Notch signaling and increased proliferation and differentiation. Enhanced Notch signaling could enhance the proliferation and differentiation of hBMSCs from patients with postmenopausal osteoporosis (OP-hBMSCs). Our results demonstrated that estrogen preserved bone mass partly by activating the Notch signaling. Because long-term ERT has been associated with several side effects, the Notch signaling could be a potential target for treating postmenopausal osteoporosis.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estrogênios/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoporose Pós-Menopausa/patologia , Receptores Notch/metabolismo , Adulto , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Pessoa de Meia-Idade , Transdução de SinaisRESUMO
OBJECTIVE: To evaluate contrast-enhanced ultrasonography (CEUS) in detecting testicular perfusion in acute testis contusion. METHODS: We established the model of testis contusion in 11 healthy male New Zealand rabbits by randomly hitting one side of the scrotum under general anesthesia. We examined the bilateral scrotums of all the animals before, immediately after and at 2, 4 and 6 hours after modeling by color Doppler flow imaging (CDFI) and CEUS, and analyzed the time-intensity curve (TIC), arriving time (AT), time to peak intensity (TTP), peak intensity (PI), half time of descending peak intensity (HT) and area under the curve (AUC) in the healthy and injured testis, respectively. RESULTS: CEUS exhibited a higher sensitivity in detecting tissue perfusion than CDFI. The mode of contrast agent perfusion in testicular contusion was fast in and slow out. There were no evident differences between the contused and the healthy testis in AT, TTP and PI before modeling. The contused testis showed significantly earlier AT and TTP, higher PI and larger AUC (P < 0.05) than the healthy one at different time points after modeling, but no statistically significant difference was found in HT (P > 0.05). CONCLUSION: Accurate parameters of testicular perfusion in acute testis contusion can be quantitatively obtained by CEUS, which are of important value for the diagnosis of testis contusion.
Assuntos
Contusões/diagnóstico por imagem , Testículo/diagnóstico por imagem , Animais , Meios de Contraste , Masculino , Coelhos , Testículo/irrigação sanguínea , Testículo/lesões , Ultrassonografia Doppler em CoresRESUMO
OBJECTIVE: To explore the incidence and risk factors of readmission of elderly patients with hip fracture after hip hemiarthroplasty. METHODS: A retrospective analysis of 237 elderly hip fracture patients who underwent hip hemiarthroplasty from February 2015 to October 2020 were performed. According to the readmission status of the patients at 3 months postoperatively, the patients were divided into readmission group (39 cases)and non-readmission group(198 cases). In readmission group, there were 7 males and 32 females with an average age of(84.59±4.34) years old, respectively, there were 34 males and 164 females with average age of (84.65±4.17) years old in non-readmission group. The general information, surgical status, hip Harris score and complications of patients in two groups were included in univariate analysis, and multivariate Logistic regression was used to analyze independent risk factors of patients' readmission. RESULTS: The proportion of complications(cerebral infarction and coronary heart disease) in readmission group was significantly higher than that of non-readmission group (P<0.05), and intraoperative blood loss in readmission group was significantly higher than that of non-readmission group(P<0.05). Harris score of hip joint was significantly lower than that of non-readmission group(P<0.05). The proportion of infection, delirium, joint dislocation, anemia and venous thrombosis in readmission group were significantly higher than that of non-readmission group (all P<0.05). Multivariate Logistic regression analysis showed that the risk factors for readmission of elderly patients with hip fracture after hip hemiarthroplasty included cerebral infarction, infection, delirium, dislocation, anemia and venous thrombosis (all P<0.05). CONCLUSION: The complications of the elderly patients who were readmission after hip hemiarthroplasty for hip fractures were significantly higher than those who were non-readmission. Cerebral infarction, infection, delirium, dislocation, anemia and venous thrombosis are risk factors that lead to patient readmission. Corresponding intervention measures can be taken clinically based on these risk factors to reduce the incidence of patient readmissions.
Assuntos
Artroplastia de Quadril , Delírio , Fraturas do Colo Femoral , Hemiartroplastia , Fraturas do Quadril , Luxações Articulares , Idoso , Idoso de 80 Anos ou mais , Infarto Cerebral/etiologia , Infarto Cerebral/cirurgia , Feminino , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/efeitos adversos , Fraturas do Quadril/etiologia , Fraturas do Quadril/cirurgia , Humanos , Luxações Articulares/cirurgia , Masculino , Readmissão do Paciente , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
The essential role of GAPDH/Siah1 signaling pathway in the pathogenesis of various injurious conditions such as traumatic spinal cord injury (SCI) has been gradually recognized. However, the drugs targeting this signaling pathway are still lacking. The endocannabinoid system, including its receptors (CB1 and CB2), act as neuroprotective and immunomodulatory modulators in SCI. WIN55212-2, an agonist for CB1 and CB2 receptors, has been demonstrated with anti-inflammatory and anti-apoptotic effects in multiple neurological diseases. Therefore, the present study aimed to investigate whether WIN55212-2 could promote functional recovery after traumatic SCI via inhibition of the GAPDH/Siah1 signaling. The traumatic SCI was induced by dropping a 10-g impactor from 25mm on the dorsal surface of T9 and T10. Our results showed that WIN55212-2 alleviated the activation of GAPDH/Siah1 signaling pathway after SCI, as indicated by the reduction in GAPDH nuclear expression, GAPDH-Siah1 complex formation and iNOS protein expression. Furthermore, WIN55212-2 reduced apoptosis, production of IL-1ß and TNF-α and activation of NF-κB signaling in the spinal cord after SCI. The behavioral tests showed that WIN55212-2 improved the functional recovery after traumatic SCI as indicated by sustained increase in the locomotor scores. However, these neuroprotective effects of WIN55212-2 were blocked in the presence of the combined treatment of AM630 (an antagonist of CB2) rather than AM251 (an antagonist of CB1). In conclusion, our study indicates that, WIN55212-2 improves the functional recovery after SCI via inhibition of GAPDH/Siah1 cascades in a CB2 receptor dependent manner, indicative of its therapeutic potential for traumatic SCI or other traumatic conditions.
Assuntos
Benzoxazinas/farmacologia , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/antagonistas & inibidores , Morfolinas/farmacologia , Naftalenos/farmacologia , Proteínas Nucleares/antagonistas & inibidores , Receptor CB2 de Canabinoide/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Endocanabinoides/metabolismo , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Proteínas Nucleares/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
UNLABELLED: Osteoporosis is a major health problem affecting the aging population, especially in patients 65 years of age and older. The imbalance between bone formation and bone resorption is generally accepted as the essential mechanism leading to osteoporosis. In addition to the abnormal activation of osteoclast-mediated bone resorption, the dysfunction of bone marrow stromal cells (BMSCs) in mediating bone formation has been accepted as a major contributor to the progression of senile osteoporosis. RESULTS: In our study, senile osteoporotic hBMSCs displayed a decreasing capacity for proliferation and osteoblast differentiation, which was associated with the downregulation of integrin α2. Forced ectopic integrin α2 expression using a lentivirus vector reversed the dysfunction of senile osteoporotic hBMSCs. Additionally, the overexpression of integrin α2 upregulated the levels of Runx2 and Osterix. Mechanically, Western blot analyses revealed that integrin α2 phosphorylated ERK1/2 and the inactivation of ERK by PD98059 suppressed the osteoblastic differentiation of hBMSCs, suggesting that integrin α2 promotes osteoblast proliferation through the activation of ERK1/2 MAPK. CONCLUSION: Taken together, our results show that hBMSCs obtained from senile osteoporotic patients gradually lose their capability to differentiate along the osteogenic lineage and proliferate, which might be associated with the abnormal regulation of the integrin α2/ERK/Runx2 signaling pathway undergoing senile osteoporosis.