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1.
Braz. j. med. biol. res ; 54(5): e10185, 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1153547

RESUMO

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.


Assuntos
Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Núcleo Pulposo , Apoptose , Alvo Mecanístico do Complexo 1 de Rapamicina , Inflamação/tratamento farmacológico
2.
Rev. colomb. reumatol ; 27(2): 120-122, ene.-jun. 2020. graf
Artigo em Espanhol | LILACS | ID: biblio-1251645

RESUMO

RESUMEN La vértebra limbus es una rara condición poco descrita en la literatura médica. Se caracteriza por una herniación marginal intracorporal del núcleo pulposo que resulta en la separación de un fragmento óseo de forma triangular. Usualmente se presenta en niños o adolescentes, principalmente en la columna lumbar, y ocasiona dolor que, en la mayoría de los casos, mejora con el tratamiento con antiinflamatorios.


A B S T R A C T The limbus vertebra is a rare condition poorly described in the medical literature. Marginal intrabody herniation of the nucleus pulposus resulting in the separation of a triangular bone fragment. It usually occurs in children or adolescents mainly in the lumbar spine and causes pain that in most cases improves with treatment with anti-inflammatories.


Assuntos
Humanos , Criança , Adolescente , Adulto , Coluna Vertebral , Terapêutica , Dor Lombar , Osso e Ossos , Núcleo Pulposo , Anti-Inflamatórios
4.
Braz. j. med. biol. res ; 52(9): e8525, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1011614

RESUMO

Many compounds of ginsenosides show anti-inflammatory properties. However, their anti-inflammatory effects in intervertebral chondrocytes in the presence of inflammatory factors have never been shown. Increased levels of pro-inflammatory cytokines are generally associated with the degradation and death of chondrocytes; therefore, finding an effective and nontoxic substance that attenuates the inflammation is worthwhile. In this study, chondrocytes were isolated from the nucleus pulposus tissues, and the cells were treated with ginsenoside compounds and IL-1β, alone and in combination. Cell viability and death rate were assessed by CCK-8 and flow cytometry methods, respectively. PCR, western blot, and immunoprecipitation assays were performed to determine the mRNA and protein expression, and the interactions between proteins, respectively. Monomeric component of ginsenoside Rd had no toxicity at the tested range of concentrations. Furthermore, Rd suppressed the inflammatory response of chondrocytes to interleukin (IL)-1β by suppressing the increase in IL-1β, tumor necrosis factor (TNF)-α, IL-6, COX-2, and inducible nitric oxide synthase (iNOS) expression, and retarding IL-1β-induced degradation of chondrocytes by improving cell proliferation characteristics and expression of aggrecan and COL2A1. These protective effects of Rd were associated with ubiquitination of IL-1 receptor accessory protein (IL1RAP), blocking the stimulation of IL-1β to NF-κB. Bioinformatics analysis showed that NEDD4, CBL, CBLB, CBLC, and ITCH most likely target IL1RAP. Rd increased intracellular ITCH level and the amount of ITCH attaching to IL1RAP. Thus, IL1RAP ubiquitination promoted by Rd is likely to occur by up-regulation of ITCH. In summary, Rd inhibited IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Condrócitos/efeitos dos fármacos , Ginsenosídeos/farmacologia , Interleucina-1beta/efeitos dos fármacos , Proteína Acessória do Receptor de Interleucina-1/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Dinoprostona/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Dor Lombar/metabolismo , Óxido Nítrico Sintase/metabolismo , Condrócitos/citologia , Condrócitos/metabolismo , Ginsenosídeos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Agrecanas/metabolismo , Interleucina-1beta/metabolismo , Ubiquitinação , Núcleo Pulposo/citologia , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/metabolismo , Inflamação/metabolismo
5.
Arq. bras. med. vet. zootec ; 68(5): 1207-1211, set.-out. 2016. ilus
Artigo em Português | LILACS, VETINDEX | ID: biblio-827893

RESUMO

A extrusão discal aguda e não compressiva é caracterizada pela extrusão de caráter agudo/hiperagudo e não compressivo do núcleo pulposo de um disco intervertebral não degenerado. Pode ser chamada de hérnia de disco de baixo volume e alta velocidade ou explosões discais e geralmente está associado a exercícios intensos ou episódios traumáticos. O núcleo pulposo é fortemente forçado através de uma pequena fissura no ânulo fibroso dorsal, provocando uma contusão espinhal. Este relato tem como objetivo apresentar um caso de provável extrusão aguda de núcleo pulposo não compressiva. Foi atendido um cão macho, três anos e seis meses de idade, maltês, pesando 4,1kg. Como queixa principal, o proprietário relatou dificuldade locomotora e dor à manipulação há um dia, sem histórico de trauma. Foi constatada paraparesia não ambulatória de início agudo com ausência de propriocepção e dor superficial em membros pélvicos e dor à palpação epaxial da coluna toracolombar. A ressonância magnética (RM) evidenciou extensa área de hipersinal em segmento toracolombar da medula espinhal, sem sinais de compressão medular e de atenuação da intensidade do núcleo pulposo do disco intervertebral L1-L2. Foi feito diagnóstico presuntivo de mielopatia focal não compressiva com edema medular de todo segmento toracolombar, característico de uma extrusão aguda de núcleo pulposo não compressiva. Foi prescrito tratamento com anti-inflamatório esteroidal, analgésico, repouso absoluto e protocolo de reabilitação com acupuntura e fisioterapia. Após sete dias de tratamento, o animal recuperou a sensibilidade dolorosa superficial em membros pélvicos e evoluiu para paraparesia ambulatória. Os resultados deste relato sugerem que a RM pode ser útil para fazer um diagnóstico presuntivo em cães com histórico e sinais clínicos compatíveis. Além disso, o tratamento conservativo em extrusões discais não compressivas é preconizado e o paciente pode apresentar boa recuperação.(AU)


Acute and non-compressive disc extrusion is characterized by the acute character of extrusion of the nucleus pulposus without real compression of the spine. It has been called low-volume and high speed disc herniation or disc explosions, and usually is associated with an intense exercise or traumatic episode. This report aims to present a case of an acute extrusion of nucleus pulposus with no compression of the spinal cord. A 3.5 year-old male dog of the Maltes breed, weighing 4.1kg was presented at the Veterinary Hospital with locomotion disorders and pain during manipulation with no history of trauma. At the physical and neurological examination, non-ambulatory paraparesis of acute onset with absence of proprioception and superficial pain in hind limbs was found, as well as pain on palpation of epaxial thoracolumbar spine. Magnetic resonance imaging (MRI) showed extensive hyper intense area in the thoracolumbar spinal cord, with no signs of spinal cord compression, and decreased intensity of the nucleus pulposus of the L1-L2 intervertebral disc. Additionally, a spinal cord edema in all thoracolumbar segments was seen that is characteristic of an acute extrusion of non-compressive nucleus pulposus. A presumptive diagnosis of non-compressive myelopathy was assumed. The dog was prescribed steroidal anti-inflammatory, analgesic, absolute rest and rehabilitation protocol, including acupuncture and physiotherapy. The patient recovered superficial pain in the pelvic limbs and evolved into ambulatory paraparesis after seven days. The results of this report suggested that MRI can be useful for making a presumptive diagnosis in dogs with a history of compatible clinical signs. Moreover, the conservative treatment in non-compressive disc extrusions can be feasible.(AU)


Assuntos
Animais , Cães , Disco Intervertebral/patologia , Núcleo Pulposo/patologia , Traumatismos da Medula Espinal/veterinária , Espectroscopia de Ressonância Magnética
6.
Braz. j. med. biol. res ; 49(6): e5020, 2016. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951681

RESUMO

This study aims to explore the effect of microRNA-21 (miR-21) on the proliferation of human degenerated nucleus pulposus (NP) by targeting programmed cell death 4 (PDCD4) tumor suppressor. NP tissues were collected from 20 intervertebral disc degeneration (IDD) patients, and from 5 patients with traumatic spine fracture. MiR-21 expressions were tested. NP cells from IDD patients were collected and divided into blank control group, negative control group (transfected with miR-21 negative sequences), miR-21 inhibitor group (transfected with miR-21 inhibitors), miR-21 mimics group (transfected with miR-21 mimics) and PDCD4 siRNA group (transfected with PDCD4 siRNAs). Cell growth was estimated by Cell Counting Kit-8; PDCD4, MMP-2,MMP-9 mRNA expressions were evaluated by qRT-PCR; PDCD4, c-Jun and p-c-Jun expressions were tested using western blot. In IDD patients, the expressions of miR-21 and PDCD4 mRNA were respectively elevated and decreased (both P<0.05). The miR-21 expressions were positively correlated with Pfirrmann grades, but negatively correlated with PDCD4 mRNA (both P<0.001). In miR-21 inhibitor group, cell growth, MMP-2 and MMP-9 mRNA expressions, and p-c-Jun protein expressions were significantly lower, while PDCD4 mRNA and protein expressions were higher than the other groups (all P<0.05). These expressions in the PDCD4 siRNA and miR-21 mimics groups was inverted compared to that in the miR-21 inhibitor group (all P<0.05). MiR-21 could promote the proliferation of human degenerated NP cells by targeting PDCD4, increasing phosphorylation of c-Jun protein, and activating AP-1-dependent transcription of MMPs, indicating that miR-21 may be a crucial biomarker in the pathogenesis of IDD.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Proteínas de Ligação a RNA/metabolismo , MicroRNAs/metabolismo , Proliferação de Células/fisiologia , Proteínas Reguladoras de Apoptose/metabolismo , Núcleo Pulposo/metabolismo , Valores de Referência , Fatores de Tempo , Proteínas Reguladoras de Apoptose/análise
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