RESUMEN
Lumbar intervertebral disc degeneration(IDD) is a prevalent inflammatory disease caused by many proinflammatory factors, such as TNF and IL-1ß. Migration inhibitory factor (MIF) is an upstream inflammatory factor widely expressed in vivo that is associated with a variety of inflammatory diseases or malignant tumors and has potential therapeutic value in many diseases. We explored the role of MIF in intervertebral disc degeneration by regulating the content of exogenous MIF or the expression of MIF in cells. Upon inducing degeneration of nucleus pulposus (NP) cells with IL-1ß, we found that the increase in intracellular and exogenous MIF promoted the catabolism induced by proinflammatory factors in NP cells, while silencing of the MIF gene alleviated the degeneration to some extent. In a mouse model, the intervertebral disc degeneration of MIF-KO mice was significantly less than that of wild-type mice. To explore the treatment of intervertebral disc degeneration, we selected the small-molecular MIF inhibitor CPSI-1306. CPSI-1306 had a therapeutic effect on intervertebral disc degeneration in the mouse model. In summary, we believe that MIF plays an important role in intervertebral disc degeneration and is a potential therapeutic target for the treatment of intervertebral disc degeneration.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Factores Inhibidores de la Migración de Macrófagos , Núcleo Pulposo , Ratones , Animales , FN-kappa B/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Transducción de Señal/fisiología , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Núcleo Pulposo/metabolismo , Disco Intervertebral/metabolismoRESUMEN
Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.
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Traumatismos de la Rodilla , FN-kappa B , Humanos , FN-kappa B/metabolismo , Transducción de Señal , Articulación de la Rodilla/metabolismo , CondrocitosRESUMEN
Microfibrillar-associated proteins (MFAPs) are extracellular matrix glycoproteins, which play a role in microfibril assembly, elastinogenesis, and tissue homeostasis. MFAPs consist of five subfamily members, including MFAP1, MFAP2, MFAP3, MFAP4, and MFAP5. Among these, MFAP2 and MFAP5 are most closely related, and exhibit very limited amino acid sequence homology with MFAP1, MFAP3, and MFAP4. Gene expression profiling analysis reveals that MFAP2, MFAP5, and MFAP4 are specifically expressed in osteoblastic like cells, whereas MFAP1 and MFAP3 are more ubiquitously expressed, indicative of their diverse role in the tropism of tissues. Molecular structural analysis shows that each MFAP family member has distinct features, and functional evidence reveals discrete purposes of individual MFAPs. Animal studies indicate that MFAP2-deficient mice exhibit progressive osteopenia with elevated receptor activator of NF-κB ligand (RANKL) expression, whereas MFAP5-deficient mice are neutropenic, and MFAP4-deficient mice displayed emphysema-like pathology and the impaired formation of neointimal hyperplasia. Emerging data also suggest that MFAPs are involved in cancer progression and fat metabolism. Further understanding of tissue-specific pathophysiology of MFAPs might offer potential novel therapeutic targets for related diseases, such as skeletal and metabolic disorders, and cancers.
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Enfermedades Metabólicas/genética , Neoplasias/genética , Factores de Empalme de ARN/genética , Secuencia de Aminoácidos , Animales , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Humanos , Hiperplasia/genética , Neointima/genéticaRESUMEN
Whey acidic proteins (WAP) perform a diverse range of important biological functions, including proteinase activity, calcium transport and bacterial growth. The WAP four-disulphide core domain protein 1 (WFDC1) gene (also called PS20), encodes the 20 kDa prostate stromal protein (ps20), which is a member of the WAP-type four-disulphide core domain family of proteins, and exhibits characteristics of serine protease inhibitors, such as elafin and secretory leukocyte protease inhibitor. Molecular structural analysis reveals that ps20 consists of four-disulphide bonds formed by eight cysteine residues located at the carboxyl terminus of the protein. Wfdc1-null mice were found to display no overt developmental phenotype, suggesting a dispensable role in organ growth and development. However, WFDC1 was able to mediate endothelial cell migration and pericyte stabilization, which are vital for the formation of functional vascular structures. WFDC1 was also found to be downregulated in cancers and exhibited a regulatory effect on cell proliferation. In addition, it was involved in the modulation of memory T cells during human immunodeficiency virus infection. Gaining a solid understanding of the mechanisms by which WFDC1 regulates tissue homeostasis and disease processes, in a tissue specific manner, will be an important move towards the development of WFDC1/ps20 as potential therapeutic targets.
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Neoplasias/metabolismo , Neovascularización Patológica/metabolismo , Proteínas/metabolismo , Humanos , Neoplasias/patología , Neovascularización Patológica/patología , Conformación Proteica , Proteínas/química , Proteínas/genéticaRESUMEN
Current pharmacological intervention for the treatment of osteolytic bone diseases such as osteoporosis focuses on the prevention of excessive osteoclastic bone resorption but does not enhance osteoblast-mediated bone formation. In our study, we have shown that 4-iodo-6-phenylpyrimidine (4-IPP), an irreversible inhibitor of macrophage migration inhibitory factor (MIF), can inhibit receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and potentiate osteoblast-mediated mineralization and bone nodule formation in vitro. Mechanistically, 4-IPP inhibited RANKL-induced p65 phosphorylation and nuclear translocation by preventing the interaction of MIF with thioredoxin-interacting protein-p65 complexes. This led to the suppression of late osteoclast marker genes such as nuclear factor of activated T cells cytoplasmic 1, resulting in impaired osteoclast formation. In contrast, 4-IPP potentiated osteoblast differentiation and mineralization also through the inhibition of the p65/NF-κB signaling cascade. In the murine model of pathologic osteolysis induced by titanium particles, 4-IPP protected against calvarial bone destruction. Similarly, in the murine model of ovariectomy-induced osteoporosis, 4-IPP treatment ameliorated the bone loss associated with estrogen deficiency by reducing osteoclastic activities and enhancing osteoblastic bone formation. Collectively, these findings provide evidence for the pharmacological targeting of MIF for the treatment of osteolytic bone disorders.-Zheng, L., Gao, J., Jin, K., Chen, Z., Yu, W., Zhu, K., Huang, W., Liu, F., Mei, L., Lou, C., He, D. Macrophage migration inhibitory factor (MIF) inhibitor 4-IPP suppresses osteoclast formation and promotes osteoblast differentiation through the inhibition of the NF-κB signaling pathway.
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Diferenciación Celular/efectos de los fármacos , Oxidorreductasas Intramoleculares/antagonistas & inhibidores , Factores Inhibidores de la Migración de Macrófagos/antagonistas & inhibidores , FN-kappa B/metabolismo , Osteoblastos/efectos de los fármacos , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Resorción Ósea , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoblastos/citología , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteoporosis/etiología , Osteoporosis/prevención & control , Ovariectomía , Ligando RANK/metabolismoRESUMEN
A feasible and optimal axis of biomechanical and anatomic significance in axial lumbosacral interbody fusion (AxiaLIF) was designed. Using the image dataset of an adult volunteer, two groups of finite element (FE) models of the AxiaLIF, lumbosacral anterior column fixation (ACF) models and middle column fixation (MCF) models with different bone graft fusion degrees, were prospectively established, and their biomechanical differences were comparatively predicted. In addition, 3D reconstruction was performed by retrospectively collecting CT data from pelvises in 60 adult cases. Their anatomic parameters relating to two groups of models were digitally measured and statistically compared. Numerical analysis revealed that the load and the maximum stress on the screw as well as the maximum stress difference between the screw and peripheral tissues in the MCF model were reduced compared with the ACF model. These indices of both models all decreased markedly in response to the increase in the disc fusion degree. Statistical analysis revealed that the effective fixed length of the sacrum in the MCF model was increased compared with the ACF model (P < 0.05). The surgical dissection distance of presacral vessels and nerves from the axis to sacrum of the MCF model was reduced compared with the ACF model (P < 0.05). The feasible and optimal axis of biomechanical and anatomic significance of the AxiaLIF is similar to the axis of the MCF model. Disc bone graft fusions plus axial screw fixations of middle column could strengthen the biomechanical stability of the AxiaLIF model. Clin. Anat. 32:337-347, 2019. © 2018 Wiley Periodicals, Inc.
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Imagenología Tridimensional/métodos , Vértebras Lumbares/anatomía & histología , Región Lumbosacra/anatomía & histología , Modelos Anatómicos , Adulto , Fenómenos Biomecánicos , Tornillos Óseos , Simulación por Computador , Femenino , Humanos , Masculino , Persona de Mediana Edad , Huesos Pélvicos/anatomía & histología , Huesos Pélvicos/diagnóstico por imagen , Fusión Vertebral/métodos , Tomografía Computarizada por Rayos XRESUMEN
Osteoporosis (OP) is a serious metabolic disease that, due to the increased number or function of osteoclasts, results in increased bone brittleness and, therefore, fragile fracture. Some recent studies report the importance of the transforming growth factor ß (TGFß) pathway in bone homeostasis. RepSox is a small molecule inhibitor of TGFßRI that has a wide range of potential application in clinical medicine, except OP. The aim of our study is to evaluate the effects of RepSox on the differentiation and bone resorption of osteoclasts in vitro and in vivo in an ovariectomy (OVX)-induced OP model. An initial analysis showed TGFßRI messenger RNA expression in both bone samples and bone cells. In the in vitro study, RepSox inhibited the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation and bone resorption activity. Real-time polymerase chain reaction (PCR) analysis showed that RepSox suppressed osteoclastic marker gene expression in both dose-dependent and time-dependent manners. In addition, RepSox did not affect osteoblast differentiation, migration or osteoblastic-specific gene expression in vitro. Furthermore, western blot analysis indicated the underlying mechanisms of the RepSox suppression of osteoclastogenesis via the Smad3 and c-Jun N-terminal kinase/activator protein-1 (JNK/AP-1) signaling pathways. Finally, our animal experiments revealed that RepSox prevented OVX-induced bone loss in vivo. Together, our data suggest that RepSox regulates osteoclast differentiation, bone resorption, and OVX-induced OP via the suppression of the Smad3 and JNK/AP-1 pathways.
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Resorción Ósea/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Pirazoles/administración & dosificación , Piridinas/administración & dosificación , Proteína smad3/genética , Animales , Resorción Ósea/etiología , Resorción Ósea/genética , Resorción Ósea/patología , Diferenciación Celular/efectos de los fármacos , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Ratones , Osteoclastos/efectos de los fármacos , Osteoporosis/etiología , Osteoporosis/genética , Osteoporosis/patología , Ovariectomía/efectos adversos , Ligando RANK/genética , Bibliotecas de Moléculas Pequeñas/administración & dosificación , Factor de Transcripción AP-1/genética , Factor de Crecimiento Transformador beta/genéticaRESUMEN
Osteoporosis, which manifests as reduced bone mass and deteriorated bone quality, is common in the elderly population. It is characterized by persistent elevation of macrophage-associated inflammation and active osteoclast bone resorption. Currently, the roles of intracellular metabolism in regulating these processes remain unclear. In this study, we initially performed bioinformatics analysis and observed a significant increase in the proportion of M1 macrophages in bone marrow with aging. Further metabolomics analysis demonstrated a notable reduction in the expression of carnitine metabolites in aged macrophages, while carnitine was not detected in osteoclasts. During the differentiation process, osteoclasts took up carnitine synthesized by macrophages to regulate their own activity. Mechanistically, carnitine enhanced the function of Nrf2 by inhibiting the Keap1-Nrf2 interaction, reducing the proteasome-dependent ubiquitination and degradation of Nrf2. In silico molecular ligand docking analysis of the interaction between carnitine and Keap1 showed that carnitine binds to Keap1 to stabilize Nrf2 and enhance its function. In this study, we found that the decrease in carnitine levels in aging macrophages causes overactivation of osteoclasts, ultimately leading to osteoporosis. A decrease in serum carnitine levels in patients with osteoporosis was found to have good diagnostic and predictive value. Moreover, supplementation with carnitine was shown to be effective in the treatment of osteoporosis.
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Resorción Ósea , Osteoporosis , Humanos , Anciano , Osteogénesis/genética , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Carnitina/metabolismo , Transducción de Señal , Osteoclastos/metabolismo , Macrófagos/metabolismo , Resorción Ósea/complicaciones , Resorción Ósea/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/genética , Ligando RANK/farmacologíaRESUMEN
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degeneration and subchondral bone remodelling. Currently, conservative treatment strategies cannot effectively alleviate the progression of OA. In this study, we used computer network analysis to show that Nitisinone (NTBC) is closely related to extracellular matrix degradation in OA and mainly interferes with the TNF-α signaling pathway. NTBC is an orphan drug used to treat hereditary type I tyrosinemia by altering phenylalanine/tyrosine metabolic flow. In this study, we found that NTBC effectively reduced chondrocyte inflammation and extracellular matrix degradation induced by TNF-α. Mechanistically, NTBC inhibited the cGAS/STING signaling pathway and reduced activation of the STING-dependent NF-κB pathway to alleviate inflammation. In addition, NTBC inhibited osteoclastogenesis and delayed the occurrence of subchondral bone remodelling. In mice with ACLT-induced osteoarthritis, intra-articular injection of NTBC significantly reduced cartilage degradation and subchondral bone remodelling. NTBC showed impressive therapeutic efficacy as a potential pharmaceutical intervention for the treatment of OA.
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Cartílago Articular , Ciclohexanonas , Nitrobenzoatos , Osteoartritis , Ratones , Animales , FN-kappa B/metabolismo , Osteogénesis , Factor de Necrosis Tumoral alfa/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Inflamación/tratamiento farmacológico , CondrocitosRESUMEN
PURPOSE: The impact of percutaneous internal fixation as a supplement to percutaneous kyphoplasty (PKP) for the management of thoracolumbar burst fractures in elderly patients is unclear. We conducted a clinical controlled trial to investigate the effect and outcomes of this technique in such patients. METHODS: Forty-three patients over 65 years old with thoracolumbar burst fractures without nerve injuries were enrolled. They were randomly assigned to treatment with simple PKP (control group, n = 22) or percutaneous short-segment pedicle screw internal fixation with PKP (treatment group, n = 21). The patients were followed for at least 2 years postoperatively and were assessed with regard to clinical and radiological outcomes. Clinical outcomes were evaluated mainly with use of visual analog scale (VAS) for pain and the Oswestry Disability Index (ODI) questionnaire. Radiological outcomes were assessed mainly on the basis of Cobb kyphosis angle and loss of kyphosis correction. RESULTS: There were no significant differences between the two groups with regard to preoperative indices. The treatment group had better VAS scores and greater postoperative improvement on the ODI compared with the control group (P < 0.05). Postoperative kyphosis angle correction in the treatment group was superior to that in the control group, and loss of correction postoperatively was significantly less (P < 0.05). In the control group, two patients suffered refractures of the injured vertebra postoperatively and one had a fracture in the adjacent vertebra. No postoperative complications needing management were noted in either group. CONCLUSIONS: Compared with simple PKP, percutaneous internal fixation with PKP is a valuable surgical option for the treatment of selected elderly patients with thoracolumbar burst fractures.
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Cifoplastia/métodos , Vértebras Lumbares/cirugía , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Anciano , Anciano de 80 o más Años , Tornillos Óseos , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas/métodos , Humanos , Cifoplastia/efectos adversos , Cifoplastia/instrumentación , Cifosis/patología , Cifosis/cirugía , Vértebras Lumbares/lesiones , Imagen por Resonancia Magnética , Masculino , Dimensión del Dolor , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Fracturas de la Columna Vertebral/patología , Vértebras Torácicas/lesiones , Resultado del TratamientoRESUMEN
Objectives: Recently, studies on microRNAs (miRNAs) and their targets and related genes have provided new therapeutic opportunities for controlling intervertebral disc degeneration (IDD). We aimed to investigate the effects of miR-148a-3p overexpression on IDD progression. Materials and Methods: This study used microRNA microarrays to analyze key regulators of IDD. Q-PCR was used to verify the IL-1ß-induced down-regulation of miR-148a-3p expression both in nucleus pulposus (NP) tissues of IDD patients and in degenerated NP cells (NPCs) of rats. Rat NPC micromass cultures and ex vivo intervertebral disc (IVD) culture models were established, and histological staining was performed to verify the effect of miR-148a-3p on the general morphology and proteoglycan and collagen contents of IVDs. In addition, q-PCR and western blotting analyses were performed to examine the expression of ECM molecules and matrix-degrading enzymes. A luciferase reporter assay was used to confirm the target genes of miR-148a-3p. Results: Our data revealed that miR-148a-3p was down-regulated in IDD. Overexpression of miR-148a-3p had no effect on ACAN or COL2A1 gene expression but decreased MMP3, MMP13, and ADAMTS5 gene expression. The matrix deposited by miR-148a-3p-overexpressing rat NPCs contained high levels of proteoglycans and collagen. The ex vivo experiments verified that agomiR-148a-3p alleviated the NPC matrix degradation induced by IL-1ß. A luciferase reporter assay confirmed that miR-148a-3p directly targeted ADAMTS5 and MMP13. Conclusion: We proved that miR-148a-3p can attenuate ECM loss and protect NP function by inhibiting matrix-degrading enzymes.
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STUDY DESIGN: A retrospective study of prospectively collected radiographic and clinical data. OBJECTIVE: This study aims to investigate the relationship between endplate morphology parameters and the incidence of cage subsidence in patients with mini-open single-level oblique lateral lumbar interbody fusion (OLIF). METHODS: We included 119 inpatients who underwent OLIF from February 2015 to December 2017. A total of 119 patients with single treatment level of OLIF were included. Plain anteroposterior and lateral radiograph were taken preoperatively, postoperatively, and during follow-up. The correlation between disc height, endplate concave angle/depth, cage position and cage subsidence were investigated. Functional rating index (Visual Analogue Scale for pain, and Roland Morris Disability Questionnaire) were employed to assess clinical outcomes. RESULTS: Cage subsidence was more commonly seen at the superior endplates (42/119, 35.29%) than at the inferior endplates (6/119, 5.04%) (p < 0.01). More importantly, cage subsidence was significantly less in patients with superior endplates that were without concave angle (3/20, 15%) than with concave angle (37/99, 37.37%) (p < 0.05). Cage subsidence correlated negatively with preoperative anterior disc height (r = -0.21, p < 0.05), but positively with disc distraction rate (r = 0.27, p < 0.01). Lastly, the distance of cage to the anterior edges of the vertebral body showed a positive correlation (r = 0.26, p < 0.01). CONCLUSIONS: This study for the first time demonstrated that endplate morphology correlates with cage subsidence after OLIF. Since relatively flat endplates with smaller concave angle significantly diminish the incidence of subsidence, the morphology of cage surface should be taken into consideration when designing the next generation of cage. In addition, precise measurement of the disc height to avoid over-distraction, and more anteriorly placement of the cage is suggested to reduce subsidence.
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OBJECTIVE: To explore the clinical effect of percutaneous endoscopic lumbar discectomy in the treatment of adjacent segment lumbar disc herniation after lumbar fusion. METHODS: From February 2010 to June 2018, 64 patients with adjacent segment lumbar disc herniation after lumbar fusion were retrospectively analyzed and divided into observation group and control group. In observation group, there were 23 males and 10 females performed with percutaneous endoscopic lumbar discectomy, including 27 cases of single segment fusion and 6 cases of double segment fusion, aged from 55 to 83 years old with an average of (65.7±7.4) years old. In control group, there were 22 males and 9 females performed with traditional open fusion revision, including 25 cases of single-segment fusion and 6 cases of double segment fusion, aged from 51 to 78 years old with an average of(64.8±7.8) years old. The operative time, intraoperative blood loss, fluoroscopy times, postoperative ambulation time and length of postoperative hospital stay were recorded. The clinical efficacy was evaluated by visual analogue scale(VAS) and Oswestry Disability Index(ODI). The complications between two groups were observed. RESULTS: All patients were followed up for at least 2 years. The observation group patients were followed up with an average of (2.4±0.5) years. The control group patients were followed up with an average of(2.6±0.7) years. Compared with control group, operation time, intraoperative blood loss, postoperative ambulation time and length of postoperative hospital stay of the observation group were significantly reduced (P<0.05), and the fluoroscopy times of observation group were significantly increased compared with control group(P<0.05). The VAS of low back and lower limb, and ODI at the latest follow-up between two groups were all significantly improved compared to those of pre-operation (P<0.05). The VAS of low back at each point and ODI at 1, 3 months after operation in observation group was significantly reduced compared with control group(P<0.05), however there was no significant difference in VAS for lower limb between two groups (P>0.05). The difference of complications between two groups was statistically significant (P<0.05). CONCLUSION: Compared with traditional open fusion revision surgery, percutaneous endoscopic lumbar discectomy for the treatment of adjacent segment lumbar disc herniation after lumbar fusion has the advantages of reducing operation time and intra-operative blood loss, shortening ambulation time and the length of postoperative hospital stay, and promoting pain and functional improvement, and decrease incidence of complications. However, long-term clinical efficacy needs further study.
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Discectomía Percutánea , Degeneración del Disco Intervertebral , Desplazamiento del Disco Intervertebral , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Discectomía , Endoscopía , Femenino , Humanos , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objective: We evaluated the effect of a novel modified OLIF technique (anteroinferior psoas approach, AIPA) for anterior decompression reconstruction in lumbar burst fractures, and compared the clinical, radiological outcomes and approach-related complications with the mini-open, lateral transpsoas approach (LTPA). Methods: From March 2016 to November 2019, 68 patients with lumbar burst fractures underwent one-stage monosegmental posterior/anterior surgery from L1-L4 segments. 35 patients included in AIPA and 33 patients in LTPA group underwent anterior decompression reconstruction. The clinical, radiological and functional evaluation outcomes were recorded during the 16-60 months follow-up period. Results: At the latest follow up, neurological state of one or more ASIA grades were achieved in AIPA (90.9%) and LTPA group (94.9%). No significant differences were noted between the two groups regarding preoperative and postoperative Cobbs angle. The surgery time (192.29 vs. 230.47 min, P = 0.02) in AIPA group was better compared with LTPA. The AIPA showed better improvement on Oswestry Disability Index (43.4% vs. 60.8%, P < 0.05) and Mental Component Score (49.0% vs. 43.7%, P < 0.05) one month after surgery, but no difference at the latest follow-up. 10 patients (9 in LTPA and 1 in AIPA) experienced temporary motor deficits in hip flexor and groin or thigh numbness, which disappeared six months after surgery. Conclusions: Compared with lateral transpsoas approach, anterior decompression reconstruction via mini-open, anteroinferior psoas approach was a safe and less invasive approach, with fewer approach-related complications in the treatment for unstable lumbar burst fractures.
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Bone metabolic homeostasis is largely dependent on the dynamic balance between osteoblasts and osteoclasts. MicroRNAs (miRNAs) play critical roles in regulating bone metabolism. In this study, we explored the role of a new miRNA (miR-148a) in osteoporosis. We compared the bone phenotype between miR-148a knockout (KO) mice and the wild-type (WT) littermates. We found miR-148a KO mice exhibited an increased bone mass phenotype and decreased osteoclastogenesis compared to the WT group. In vitro, miR-148a overexpression promoted osteoclastogenesis and bone resorption function. Mechanistically, NRP1 was identified as a novel direct target of miR-148a, and NRP1 silencing reversed the effect of miR-148a knockout. In OVX and calvarial osteolysis models, miR-148a KO protects mice against excessive bone resorption, while miR-148a agomiR/AAV-shNRP1 accelerates pathologic bone loss. Finally, the miR-148a level was found to be positively correlated with ß-CTX in postmenopausal osteoporosis (PMOP) serum specimens. In summary, our findings revealed that miR-148a genetic deletion ameliorates bone loss under physiological and pathological conditions by targeting NRP1. In osteoclast-related bone metabolic diseases such as PMOP, miR-148a may be an attractive therapeutic target in the future.
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Osteoporosis is a metabolic disorder of reduced bone mass, accompanied by the deterioration of the bone microstructure, resulting in increased brittleness and easy fracture. Its pathogenesis can be explained by mainly excessive osteoclast formation or bone resorption hyperfunction. Oxidative stress is intricately linked with bone metabolism, and the maturation and bone resorption of osteoclasts respond to intracellular ROS levels. SIS3 is a small-molecule compound that selectively suppresses Smad3 phosphorylation in the TGF-ß/Smad signaling pathway and attenuates the ability to bind to target DNA. Several studies have reported that Smad3 plays a significant role in bone metabolism. However, whether SIS3 can modulate bone metabolism by affecting osteoclastogenesis and the specific molecular mechanisms involved remain unknown. Here, we demonstrated that SIS3 could suppress osteoclastogenesis and ameliorate bone loss in ovariectomized mice. Mechanistically, SIS3 inhibited Smad3 phosphorylation in BMMs, and the deficiency of phosphorylated Smad3 downregulated ROS production and Nox4-dependent expression during osteoclast formation, thereby blocking MAPK phosphorylation and the synthesis of downstream osteoclast marker proteins. Similarly, Nox4 plasmid transfection significantly alleviated osteoclast formation inhibited by SIS3. In addition, we identified the interaction region between Smad3 and Nox4 by ChIP and dual luciferase reporter assays. Collectively, we found that SIS3 could inhibit Smad3 phosphorylation, reduce Nox4-dependent ROS generation induced by RANKL, and prevent osteoclast differentiation and maturation, making it a promising alternative therapy for osteoporosis.
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Resorción Ósea/prevención & control , Isoquinolinas/farmacología , NADPH Oxidasa 4/metabolismo , Osteogénesis/efectos de los fármacos , Ovariectomía , Piridinas/farmacología , Pirroles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Western Blotting , Resorción Ósea/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Células Cultivadas , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Ratones Endogámicos C57BL , Microscopía Confocal , NADPH Oxidasa 4/genética , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteogénesis/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: The aim of this retrospective study is to review our experience in the diagnosis and role of transforaminal percutaneous endoscopic discectomy (TPED) for symptomatic gas-filled discal cysts. METHODS: Between May 2014 and June 2017, 3 patients from Lishui Center Hospital (Lishui China), who underwent TPED for symptomatic gas-filled discal cysts, were analyzed. The clinical features, imaging findings, operative findings, and treatment outcomes are presented. In addition, relevant literature regarding gas-filled discal cysts was searched using PubMed, and their characteristics, clinical features, therapeutic strategies, and survival outcomes were reviewed. RESULTS: The median age of the patients was 56.7 years (range, 55-60 years). In all patients, a discal cyst was located in the lumbar region, and the patients presented with backache and numbness in the lower extremities. The diagnosis was made by lumbar 3-dimensional computed tomography (3D-CT) or magnetic resonance imaging (MRI). All patients underwent TPED. All patients recovered successfully and were eventually discharged. Eighteen articles were identified from the searches of the database, and a total of 42 patients were included. There were 28 males and 14 females. The mean age was 56.8 years, ranging from 27 to 85 years. Lower back pain was the major symptom. Twenty-two patients underwent surgery, 4 patients underwent percutaneous needle aspiration, 2 patients underwent drug therapy, 13 patients received nonoperative treatment, and 1 patient was unknown. CONCLUSION: TPED for gas-filled discal cysts is feasible, effective, and successful, although it should be performed by an experienced surgeon with awareness of the potential risk of severe nerve root injury.
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Quistes/cirugía , Discectomía Percutánea/métodos , Endoscopía/métodos , Gases/metabolismo , Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Enfermedades de la Columna Vertebral/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Quistes/metabolismo , Estudios de Factibilidad , Femenino , Humanos , Disco Intervertebral/metabolismo , Vértebras Lumbares/metabolismo , Región Lumbosacra , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades de la Columna Vertebral/metabolismo , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to compare the radiological features of intravertebral clefts (IVC) between Kümmell disease (KD) and acute osteoporotic vertebral compression fracture (OVCF). MATERIALS AND METHODS: This is a retrospective study. A total of 79 patients with IVC from January 2014 to December 2018 were included in this study. There were 22 men and 57 women, with an average of 73.5 years. Based on the exact time interval from injury to treatment and the pathological examination results, the patients were divided into KD group (44 patients) and acute OVCF group (35 patients). The two groups were compared by the margin sclerosis of IVC, vertebra and pedicle ossification, stress fracture of the spinous process, paravertebral callus, the shape of IVC, cleft in the adjacent disc, and flatness of IVC's margin from plain radiographs and computed tomography (CT). The two groups were compared by the IVC content, double-line sign, and signal of fracture vertebral from their magnetic resonance imaging (MRI). RESULTS: There were no significant differences in sex, age, and fracture distribution between the KD group and the acute OVCF group. IVC was present in both the KD group and the acute OVCF group. Six radiological features were only present in the KD group, including sclerosis of the cleft margin (95.5%, 42/44), ossification of the fractured vertebrae (100%, 44/44), ossification of the pedicle (31.8%, 14/44), double-line sign (27.3%, 12/44), stress fracture of the spinous process (13.6%, 6/44), and even formation of paravertebral callus (18.2%, 8/44). Although there were statistical differences in the other four radiological features of content of IVC (P = 0.02), cleft sign in adjacent intervertebral disc (P < 0.01), margin of IVC (P = 0.02), and the shape of IVC (P = 0.01) between the KD group and acute OVCF group, these characteristics could be found in both groups. CONCLUSION: IVC could present in patients with both KD and acute OVCF; however, we found that marginal cleft sclerosis, vertebral and pedicle ossification, double-line sign, spinous process fracture, and formation of paravertebral callus are unique radiological features of KD and could be used for differentiation of KD from acute OVCF with IVC.
Asunto(s)
Fracturas por Compresión/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Radiografía , Estudios RetrospectivosRESUMEN
ABSTRACT: Osteosarcoma is a malignant tumor that develops from a mesenchymal cell line and is caused by gene-environment interactions. This study aimed to explore whether TIMP2/TIMP3 polymorphisms influenced the osteosarcoma risk.The expression of the TIMP2 and TIMP3 genes in osteosarcoma histiocytes was analyzed by immunohistochemistry. In this case-control study, which includes samples from 499 patients and 500 healthy controls, 10 single-nucleotide polymorphisms (SNPs) in TIMP2 and TIMP3 were selected. Furthermore, we used the Agena MassARRAY platform for genotyping. The statistical analysis was performed using χ2 test/Fisher exact test, and logistic regression analysis.The immunohistochemistry results showed that the expression of TIMP2 is obvious higher in osteosarcoma histiocytes than in the normal histiocytes. The association study indicated that the allele of rs2277698 and rs4789936 were protective SNPs reducing the risk of osteosarcoma (odds ratios â>â1, Pâ<â.05) by the χ2 test. In the genetic model, logistic regression analyses revealed that the rs2277698 and rs4789936 were associated with decreasing the risk of osteosarcoma under the codominant model, dominant model, and log-additive model. Stratification analysis revealed that 2 SNPs (rs2277698 and rs4789936) were significantly associated with a reduced risk of osteosarcoma in allele and genetic model after stratification by gender or age (Pâ<â.05). In addition, the haplotype "Trs2277698Crs2009169Crs7342880" of TIMP2 was associated with decreasing the osteosarcoma risk. The "Ars9609634Trs11547635" of TIMP3 was associated with reducing the osteosarcoma risk.This finding shed new light on the high expression of TIMP2 polymorphisms may contribute to decreasing the osteosarcoma risk in Zhejiang populations.
Asunto(s)
Pueblo Asiatico/genética , Neoplasias Óseas/genética , Osteosarcoma/genética , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-3/genética , Adolescente , Anciano , Alelos , Neoplasias Óseas/etnología , Estudios de Casos y Controles , China/etnología , Femenino , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad/etnología , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos , Humanos , Inmunohistoquímica , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Osteosarcoma/etnología , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Adulto JovenRESUMEN
Osteosarcoma (OS) is the most common malignant bone tumor and the longterm survival rates remain unsatisfactory. Transforming growth factorß (TGFß) has been revealed to play a crucial role in OS progression, and RepSox is an effective TGFß inhibitor. In the present study, the effect of RepSox on the proliferation of the OS cell lines (HOS and 143B) was detected. The results revealed that RepSox effectively inhibited the proliferation of OS cells by inducing Sphase arrest and apoptosis. Moreover, the inhibitory effect of RepSox on cell migration and invasion was confirmed by woundhealing and Transwell assays. Furthermore, western blotting revealed that the protein levels of molecules associated with the epithelialmesenchymal transition (EMT) phenotype, including Ecadherin, Ncadherin, Vimentin, matrix metalloproteinase (MMP)2 and MMP9, were reduced by RepSox treatment. Concurrently, it was also revealed that the JNK and Smad3 signaling pathway was inhibited. Our in vivo findings using a xenograft model also revealed that RepSox markedly inhibited the growth of tumors. In general, our data demonstrated that RepSox suppressed OS proliferation, EMT and promoted apoptosis by inhibiting the JNK/Smad3 signaling pathway. Thus, RepSox may be a potential antiOS drug.