RESUMEN
Intervertebral disc degeneration (IDD) is a high incidence disease of musculoskeletal system that often leads to stenosis, instability, pain and even deformity of the spinal segments. IDD is an important cause of discogenic lower back pain and often leads to large economic burden to families and society. Currently, the treatment of IDD is aimed at alleviating symptoms rather than blocking or reversing pathological progression of the damaged intervertebral disc. Resveratrol (RSV) is a polyphenol phytoalexin first extracted from the Veratrum grandiflflorum O. Loes and can be found in various plants and red wine. Owing to the in-depth study of pharmacological mechanisms, the therapeutic potential of RSV in various diseases such as osteoarthritis, neurodegenerative diseases, cardiovascular diseases and diabetes have attracted the attention of many researchers. RSV has anti-apoptotic, anti-senescent, anti-inflammatory, anti-oxidative, and anabolic activities, which can prevent further degeneration of intervertebral disc cells and enhance their regeneration. With high safety and various biological functions, RSV might be a promising candidate for the treatment of IDD. This review summarizes the biological functions of RSV in the treatment of IDD and to facilitate further research.
Asunto(s)
Degeneración del Disco Intervertebral , Humanos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Resveratrol/farmacología , Resveratrol/uso terapéuticoRESUMEN
Lumbar disc herniation is a common disease characterized by the degeneration of intervertebral discs (IVDs), accompanied by imbalance of metabolic and inflammatory homeostasis. Current studies establish that IVD degeneration is induced by increased apoptosis of nucleus pulposus (NP) cells. However, the underlying mechanisms of NP cell survival/apoptosis are not well elucidated. Here, we reveal a novel mechanism by which mTORC1 signaling controls NP cell survival through regulating metabolic homeostasis. We demonstrated that hyperactivated mTORC1 activity induced by inflammatory cytokines engenders the apoptosis of NP cells, whereas pharmacological inhibition of mTORC1 activity promotes NP cell survival. Using an integrative approach spanning metabolomics and biochemical approaches, we showed that mTORC1 activation enhanced glucose metabolism and lactic acid production, and therefore caused NP cell apoptosis. Our study identified mTORC1 in NP cells as a novel target for IVD degeneration, and provided potential strategies for clinical intervention of lumbar disc herniation.
Asunto(s)
Degeneración del Disco Intervertebral , Núcleo Pulposo , Apoptosis , Humanos , Inflamación/tratamiento farmacológico , Degeneración del Disco Intervertebral/tratamiento farmacológico , Diana Mecanicista del Complejo 1 de la RapamicinaRESUMEN
Lumbar disc herniation is a common disease characterized by the degeneration of intervertebral discs (IVDs), accompanied by imbalance of metabolic and inflammatory homeostasis. Current studies establish that IVD degeneration is induced by increased apoptosis of nucleus pulposus (NP) cells. However, the underlying mechanisms of NP cell survival/apoptosis are not well elucidated. Here, we reveal a novel mechanism by which mTORC1 signaling controls NP cell survival through regulating metabolic homeostasis. We demonstrated that hyperactivated mTORC1 activity induced by inflammatory cytokines engenders the apoptosis of NP cells, whereas pharmacological inhibition of mTORC1 activity promotes NP cell survival. Using an integrative approach spanning metabolomics and biochemical approaches, we showed that mTORC1 activation enhanced glucose metabolism and lactic acid production, and therefore caused NP cell apoptosis. Our study identified mTORC1 in NP cells as a novel target for IVD degeneration, and provided potential strategies for clinical intervention of lumbar disc herniation.
Asunto(s)
Humanos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Núcleo Pulposo , Apoptosis , Diana Mecanicista del Complejo 1 de la Rapamicina , Inflamación/tratamiento farmacológicoRESUMEN
This study aimed to identify dogs with presumptive diagnosis of cervical intervertebral disc disease (IVDD) submitted to clinical management and to evaluate the outcomes. Data were obtained from the medical records of patients with neurological dysfunction assisted at a University Veterinary Hospital from 2006 to 2017. In addition to the patients' records, dog owners responded to a questionnaire on the success of therapy. Four hundred and thirteen neurological records were evaluated, and 164 met the inclusion criteria of the study. The most common breed was Dachshund, followed by mongrels. Classification of neurological dysfunction in the study sample was as follows: 15.9% with grade I, 25.6% with grade II, 26.8% with grade III, 8.5% with grade IV, and 23.2% with grade V. Outcome was satisfactory in 71.6% of the dogs and unsatisfactory in 28.4% of them. Recurrence was observed in 27.7% of those with satisfactory outcomes. The clinical treatment of dogs with thoracolumbar IVDD is satisfactory, particularly for animals with milder disease grades (I, II, and III). There is possibility of recurrence with conservative therapy and clinical signs may be more severe.(AU)
O objetivo desse estudo foi identificar cães com diagnóstico presuntivo de DDIV toracolombar submetidos ao tratamento clínico, a fim de avaliar a resposta à terapia instituída. Foram revisados os registros neurológicos de cães atendidos pelo Serviço de Neurologia e Neurocirurgia Veterinária no período de 2006 a 2017 de um Hospital Veterinário Universitário. Foi realizada coleta de dados a partir dos registros e por meio de um questionário respondido pelos tutores. Foram avaliadas 413 fichas neurológicas de cães e obtidas informações para inclusão no estudo em 164 delas. As raças mais frequentes foram dachshunds, seguido de cães sem raça definida. Quanto ao grau de disfunção neurológica foi definido como grau I para 15,9% dos cães, grau II para 25,6%, grau III para 26,8%, grau IV para 8,5% e grau V para 23,2%. A recuperação foi satisfatória em 71,6% dos cães e insatisfatória em 28,4%. Dos que se recuperaram satisfatoriamente, 27,7% tiveram recidivas. Com base nos resultados obtidos pode-se concluir que o tratamento clínico em repouso absoluto e administração de anti-inflamatórios e analgésicos opióides para cães com DDIV toracolombar é efetivo, principalmente para cães em graus mais leves da doença (grau I, II e III). Há possibilidade de recidiva com esse tipo de terapia cujos sinais clínicos poderão ser mais graves.(AU)
Asunto(s)
Animales , Perros , Compresión de la Médula Espinal/tratamiento farmacológico , Compresión de la Médula Espinal/terapia , Compresión de la Médula Espinal/veterinaria , Enfermedades de la Columna Vertebral/tratamiento farmacológico , Enfermedades de la Columna Vertebral/terapia , Enfermedades de la Columna Vertebral/veterinaria , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/veterinaria , Disco Intervertebral/patologíaRESUMEN
This study aimed to identify dogs with presumptive diagnosis of cervical intervertebral disc disease (IVDD) submitted to clinical management and to evaluate the outcomes. Data were obtained from the medical records of patients with neurological dysfunction assisted at a University Veterinary Hospital from 2006 to 2017. In addition to the patients' records, dog owners responded to a questionnaire on the success of therapy. Four hundred and thirteen neurological records were evaluated, and 164 met the inclusion criteria of the study. The most common breed was Dachshund, followed by mongrels. Classification of neurological dysfunction in the study sample was as follows: 15.9% with grade I, 25.6% with grade II, 26.8% with grade III, 8.5% with grade IV, and 23.2% with grade V. Outcome was satisfactory in 71.6% of the dogs and unsatisfactory in 28.4% of them. Recurrence was observed in 27.7% of those with satisfactory outcomes. The clinical treatment of dogs with thoracolumbar IVDD is satisfactory, particularly for animals with milder disease grades (I, II, and III). There is possibility of recurrence with conservative therapy and clinical signs may be more severe.(AU)
O objetivo desse estudo foi identificar cães com diagnóstico presuntivo de DDIV toracolombar submetidos ao tratamento clínico, a fim de avaliar a resposta à terapia instituída. Foram revisados os registros neurológicos de cães atendidos pelo Serviço de Neurologia e Neurocirurgia Veterinária no período de 2006 a 2017 de um Hospital Veterinário Universitário. Foi realizada coleta de dados a partir dos registros e por meio de um questionário respondido pelos tutores. Foram avaliadas 413 fichas neurológicas de cães e obtidas informações para inclusão no estudo em 164 delas. As raças mais frequentes foram dachshunds, seguido de cães sem raça definida. Quanto ao grau de disfunção neurológica foi definido como grau I para 15,9% dos cães, grau II para 25,6%, grau III para 26,8%, grau IV para 8,5% e grau V para 23,2%. A recuperação foi satisfatória em 71,6% dos cães e insatisfatória em 28,4%. Dos que se recuperaram satisfatoriamente, 27,7% tiveram recidivas. Com base nos resultados obtidos pode-se concluir que o tratamento clínico em repouso absoluto e administração de anti-inflamatórios e analgésicos opióides para cães com DDIV toracolombar é efetivo, principalmente para cães em graus mais leves da doença (grau I, II e III). Há possibilidade de recidiva com esse tipo de terapia cujos sinais clínicos poderão ser mais graves.(AU)
Asunto(s)
Animales , Perros , Compresión de la Médula Espinal/tratamiento farmacológico , Compresión de la Médula Espinal/terapia , Compresión de la Médula Espinal/veterinaria , Enfermedades de la Columna Vertebral/tratamiento farmacológico , Enfermedades de la Columna Vertebral/terapia , Enfermedades de la Columna Vertebral/veterinaria , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/veterinaria , Disco Intervertebral/patologíaRESUMEN
STUDY DESIGN: Laboratory study. OBJECTIVE: Evaluate the effect of substance P (SP) on an intervertebral disc rat organ culture model. SUMMARY OF BACKGROUND DATA: Monolayer cell experiments have demonstrated that exposure intervertebral disc tissue cells to SP leads to upregulation in inflammatory cytokine expression; however, this has not been evaluated in a more complex organ culture model. METHODS: Forty-eight intervertebral discs from eight rats were used in an organ culture model. Intervertebral discs were divided into three groups: control, SP-treated group, and a group treated with an SP antagonist followed by SP. Cytokine antibody array was used to quantify expression patterns, which were confirmed using ELISA and real-time polymerase chain reaction. RESULTS: The cytokine array demonstrated a 3.40â±â 0.59-fold increase in interleukin 6 (IL-6) expression in the SP group (Pâ=â0.004), and the effect of SP was mitigated by the SP antagonist (Pâ=â0.03). These results were verified as ELISA demonstrated a significant difference in the IL-6 level between the control group and SP group (0.73 vs. 5.80 ng/mL, Pâ<â0.001), and there was a significant difference in the IL-6 level between the SP and the SP antagonist group (5.80 vs. 4.02 ng/mL, Pâ=â0.01). Similarly, the real-time polymerase chain reaction demonstrated that the discs treated with SP had a 4.77-fold increase in IL-6 levels (Pâ=â0.01) compared to controls, and a significantly greater increase in IL-6 levels between the intervertebral discs in the SP group and those in the SP antagonist group versus control (4.77 vs. 1.57, Pâ=â0.02). CONCLUSION: SP lead to the activation of an inflammatory pathway by increasing expression of IL-6 in an intervertebral disc organ culture model. These results provide evidence that SP may be an important factor in the link between intervertebral disc degeneration and low back pain. LEVEL OF EVIDENCE: N/A.
Asunto(s)
Citocinas/metabolismo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Disco Intervertebral/efectos de los fármacos , Técnicas de Cultivo de Órganos , Sustancia P/farmacología , Animales , Células Cultivadas/efectos de los fármacos , Interleucina-1beta/metabolismo , Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVES: To compare the perioperative and long-term postoperative effectiveness of bone morphogenetic protein (BMP) for lumbar arthrodesis in skeletally mature adults with degenerative disk disease (DDD) to that of the current golden standard treatment, iliac crest autologous bone graft (ICBG). SUMMARY OF BACKGROUND DATA: The treatment efficacy of lumbar arthrodesis in DDD is a complex clinical and economic issue for patients and health care providers. METHODS: Comprehensive electronic literature search was performed using following databases: Ovid MEDLINE; Embase; Cochrane Library; Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects; Methodology Register; Technology Assessment Database; and Economic Evaluation Database. The full year ranges of each database until May of 2012 were included. RESULTS: Eight randomized controlled clinical trials of 383 citations were selected. The included studies involved 1138 participants. The pooled 2-year postoperative clinical outcomes were equivalent in BMP and ICBG groups, and exceeded minimum clinically important differences for Oswestry Disability Index, SF-36 (physical scale), and numeric rating scale (back pain). ICBG was associated with increased pain and complications at the donor site (P<0.01). The pooled average operative time was 21 minutes less in BMP versus ICBG (P<0.001). The pooled rate of additional surgical treatment was 2 times less in the BMP than in the ICBG groups (P=0.006). The pooled risk of nonunion at 24-month follow-up was 2 times less in the BMP than in the ICBG groups (P=0.037), however, this effect was likely biased. CONCLUSIONS: BMP, in particular rhBMP-2, is a good alternative to autogenous bone graft, especially in cases when harvesting of autologous bone is contraindicated or undesirable, operation time is limited, and there are no contraindications for BMP use.However, the current study did not reveal evidence robust enough to develop strong medical recommendations concerning BMP use for lumbar arthrodesis in degenerative disk disease.
Asunto(s)
Proteínas Morfogenéticas Óseas/uso terapéutico , Trasplante Óseo , Ilion/trasplante , Degeneración del Disco Intervertebral/tratamiento farmacológico , Vértebras Lumbares/cirugía , Atención Perioperativa , Fusión Vertebral/métodos , Adulto , Anciano , Autoinjertos , Proteínas Morfogenéticas Óseas/farmacología , Femenino , Estudios de Seguimiento , Humanos , Ilion/efectos de los fármacos , Degeneración del Disco Intervertebral/cirugía , Vértebras Lumbares/efectos de los fármacos , Región Lumbosacra/cirugía , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/etiología , Sesgo de Publicación , Proteínas Recombinantes/uso terapéutico , Fusión Vertebral/efectos adversos , Encuestas y Cuestionarios , Factor de Crecimiento Transformador beta , Resultado del TratamientoRESUMEN
STUDY DESIGN: Laboratory based controlled in vivo study. OBJECTIVE: To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration. SUMMARY OF BACKGROUND DATA: Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A Centers for Disease Control report from 2009 reported that many patients are using glucosamine supplementation for low back pain, without significant evidence to support its use. Because disc degeneration is a major contributor of low back pain, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration. METHODS: Eighteen skeletally mature New Zealand White rabbits were divided into 4 groups: control, annular puncture, glucosamine, and annular puncture + glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107 mg/d (weight based equivalent to human 1500 mg/d). Annular puncture surgery involved puncturing the annulus fibrosus of 3 lumbar discs with a 16-gauge needle to induce degeneration. Serial magnetic resonance images were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan content, relative gene expression measured by real time polymerase chain reaction, and histological analyses. RESULTS: The magnetic resonance imaging index and nucleus pulposus area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and glycosaminoglycan content. Gene expression was consistent with a detrimental effect on matrix. CONCLUSION: These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, magnetic resonance imaging, histology, and total proteoglycan is antianabolic. This raises concern about this commonly used supplement, and future research is needed to establish the clinical relevance of these findings.