RESUMEN
BACKGROUND: This study investigates the role of IGFBP3-mediated m6A modification in regulating the miR-23a-3p/SMAD5 axis and its impact on fracture healing, aiming to provide insights into potential therapeutic targets. METHODS: Utilizing fracture-related datasets, we identified m6A modification-related mRNA and predicted miR-23a-3p as a regulator of SMAD5. We established a mouse fracture healing model and conducted experiments, including Micro-CT, RT-qPCR, Alizarin Red staining, and Alkaline phosphatase (ALP) staining, to assess gene expression and osteogenic differentiation. RESULTS: IGFBP3 emerged as a crucial player in fracture healing, stabilizing miR-23a-3p through m6A modification, leading to SMAD5 downregulation. This, in turn, inhibited osteogenic differentiation and delayed fracture healing. Inhibition of IGFBP3 partially reversed through SMAD5 inhibition, restoring osteogenic differentiation and fracture healing in vivo. CONCLUSION: The IGFBP3/miR-23a-3p/SMAD5 axis plays a pivotal role in fracture healing, highlighting the relevance of m6A modification. IGFBP3's role in stabilizing miR-23a-3p expression through m6A modification offers a potential therapeutic target for enhancing fracture healing outcomes.
Asunto(s)
Adenina , Curación de Fractura , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Animales , Ratones , Adenina/análogos & derivados , Diferenciación Celular , Modelos Animales de Enfermedad , Regulación hacia Abajo , MicroARNs/genética , MicroARNs/metabolismo , Osteogénesis/fisiología , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismoRESUMEN
OBJECTIVE: To explore the clinical effect of bridging system in the treatment of severe comminuted femoral fracture. METHODS: From March 2016 to October 2018, 50 patients with severe comminuted femoral fracture including 35 males and 15 females, aged 48 to 72(54.6±8.7) years, were admitted. All cases were comminuted fractures of the femoral shaft, 16 with proximal femur fractures and 7 with distal femur fractures. All cases were all unilateral fractures, 23 on the left and 27 on the right. The time from injury to operation was 5 to 60 (26.7±13.3) hours. The cause of injury was traffic accident, 12 cases with high fall, 35 cases fell and 3 cases fell accidentally. The patients were treated with bridge combined internal fixation system, and the operative effect and fracture healing were analyzed. RESULTS: The operation was successful in all patients. There was no change to other fixed operation. The operation time was (75.8±12.3) min, the amount of bleeding was(356.4±64.8) ml, and there was no serious postoperative complications such as infection, internal fixation displacement, re fracture and nonunion. After 6 to 36 months follow-up, the fracture healing was evaluated by Warden's score. With the extension of observation time, Warden's score gradually increased, and the time of bone healing was(5.5±0.9) months. Harris score and HSS score were used to evaluate the function of hip and knee joint respectively. With the extension of time, Harris score and HSS score increased gradually. Six months after operation, Harris score was 83.5±11.2, HSS score was 79.7±10.5. During the follow-up period, there were no serious complications such as internal fixation displacement, re-fracture, nonunion of fracture and deep vein thrombosis of lower extremity. CONCLUSION: The bridge combined internalfixation system has better safety and effectiveness in the treatment of severe comminuted femoral fracture. As long as the requirements of local anatomy and biomechanics are strictly mastered and the operation risks are fully evaluated in combination with imaging, the better fixation effect can be achieved. The operation has less trauma, fewer complications and simple operation, which is believed to have a wider application potential. Due to the limited sample size and follow-up time, no clinical control was set up, the results of the study still need to be further verified by prospective trials.
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Fracturas del Fémur , Fracturas Conminutas , Anciano , Femenino , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas , Curación de Fractura , Fracturas Conminutas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The objective of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) of osteoprotegerin gene (OPG) with bone mineral density (BMD) and osteoporosis. A total of 338 Chinese postmenopausal women with primary osteoporosis and 367 healthy controls were enrolled. The lumbar spine (L2â4), total hip and femoral neck hip of BMD were assessed by dual-energy X-ray absorptiometry (DEXA). OPG genetic variants were genotyped through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), created restriction site-PCR (CRS-PCR) and DNA sequencing methods. In this study, the g.18861A>G and g.25548C>T SNPs were detected and our data suggested that the significant differences of spine BMD, femoral neck hip BMD and total hip BMD were found among different g.18861A>G genotype, subjects with the AA genotype were significantly higher than those of AG and GG genotypes (p < 0.05). The g.25548C>T variant was not significantly associated with spine BMD, femoral neck hip BMD and total hip BMD (p > 0.05), while almost reached at the significant level in total hip BMD (p = 0.061). These findings suggeste that OPG gene variants are related to BMD and osteoporosis in Chinese postmenopausal women.
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Huesos/diagnóstico por imagen , Osteoporosis Posmenopáusica/genética , Osteoprotegerina/genética , Polimorfismo de Nucleótido Simple , Absorciometría de Fotón , Anciano , Alelos , Densidad Ósea , Huesos/metabolismo , Estudios de Casos y Controles , China/epidemiología , Femenino , Cuello Femoral/diagnóstico por imagen , Frecuencia de los Genes , Estudios de Asociación Genética , Articulación de la Cadera/diagnóstico por imagen , Hospitales Urbanos , Humanos , Vértebras Lumbares/diagnóstico por imagen , Persona de Mediana Edad , Osteoporosis Posmenopáusica/diagnóstico por imagen , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/metabolismo , Osteoprotegerina/metabolismo , Factores de Riesgo , Salud UrbanaRESUMEN
The dura mater, the outermost layer of the meninges covering the brain and spinal cord, is a collagenous connective tissue consisting of numerous collagen fibers, fibroblasts, and few elastic fibers arranged in a parallel form. The dura mater may be damaged by trauma or excising during intracranial or spinal surgery., To date, cerebrospinal fluid leakage followed by dura damage is still an intractable complication due to its various secondary complications , dural repair has recently garnered increased attention with the progress of the spinal surgery and neurosurgery. In this review, we discuss commonly used methods including the addition of sealants, the use of substitutes, and other effective methods and materials.