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Article in Chinese | WPRIM | ID: wpr-928119


Traditional Chinese medicine has unique advantages in the treatment of degenerative bone and joint diseases, and its widely used in clinical practice. In recent years, many scholars have conducted a large number of basic studies on the delay of intervertebral disc degeneration by herbal compound and monomeric components from different perspectives. In order to further elucidate its mechanism of action, this paper summarizes the in vivo and in vitro experimental studies conducted at the level of both herbal compound and single components, respectively, in order to provide references for the basic research on the treatment of lumbar intervertebral disc degeneration by Chinese medicine. A summary shows that commonly used herbal compound prescriptions include both classical prescriptions such as Duhuo Jisheng Decoction, as well as clinical experience prescriptions such as Yiqi Huoxue Recipe. Angelicae Sinensis Radix, Chuanxiong Rhizoma, Rehmanniae Radix Praeparata, Achyranthis Bidentatae Radix, and Eucommiae Cortex were used most frequently. Tonic for deficiency and blood stasis activators were used most frequently. The most utilized monomeric components include icariin, ginsenoside Re, salvianolic acid B and aucubin. The main molecular mechanisms by which herbal compound and monomeric components delay of lumbar intervertebral disc degeneration include improving the intervertebral disc microenvironment, promoting the synthesis of aggregated proteoglycans and type Ⅱ collagen in the intervertebral disc, reducing the degradation of the extracellular matrix, and inhibiting apoptosis in the nucleus pulposus cells, etc. The main signaling pathways involved include Wnt/β-catenin signaling pathway, MAPK-related signaling pathway, mTOR signaling pathway, Fas/FasL signaling pathway, PI3 K/Akt signaling pathway, NF-κB signaling pathway, JAK/STAT signaling pathway, and hedgehog signaling pathway, etc.

China , Drugs, Chinese Herbal/therapeutic use , Hedgehog Proteins/metabolism , Humans , Intervertebral Disc Degeneration/metabolism , Nucleus Pulposus/metabolism , Wnt Signaling Pathway
Braz. j. med. biol. res ; 54(5): e10185, 2021. graf
Article in English | LILACS | ID: biblio-1153547


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.

Humans , Intervertebral Disc Degeneration/drug therapy , Nucleus Pulposus , Apoptosis , Mechanistic Target of Rapamycin Complex 1 , Inflammation/drug therapy
Article in Chinese | WPRIM | ID: wpr-879445


OBJECTIVE@#To investigate the expression and clinical significance of receptor interacting protein serine-threonine kinases 1 (RIPK1) in the nucleus pulposus of patients with lumbar disc herniation (LDH).@*METHODS@#Nucleus pulposus tissue specimens of 40 patients with LDH patients underwent surgical treatment from January 2016 to January 2018 as the case group, and nucleus pulposus tissue specimens of 30 patients with lumbar spine fracture underwent surgical treatment at the same time as the control group. The expression of RIPK1 mRNA and protein of receptor interaction were detected by polymerase chain reaction (PCR) and Western blot, respectively. The expression of RIPK1 protein in the nucleus pulposus were detected by immunohistochemical staining. The concentrations of RIPK1 and tumor necrosis factor-α (TNF-α) in nucleus pulposus were detected by ELISA method. The relationship between the concentrations of RIPK1, TNF-α in nucleus pulposus and the Pearce grade of LDH patients was analyzed by one-way ANOVA. The correlation between RIPK1 and TNF-α was analyzed by Pearson.@*RESULTS@#RIPK1 was weakly positively expressed in nucleus pulposus of control group, and RIPK1 protein was positively or strongly positively expressed in case group. The expression of RIPK1 mRNA in nucleus pulposus of case group was higher than that of control group (@*CONCLUSION@#The expression levels of RIPK1 mRNA and protein in the intervertebral disc tissues of LDH patients are higher than those of normal intervertebral disc tissues, and increased with the increase of Pearce grade, which may be an important factor involved in LDH inflammatory disease.

Humans , Intervertebral Disc/metabolism , Intervertebral Disc Degeneration , Intervertebral Disc Displacement/genetics , Nucleus Pulposus , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Tumor Necrosis Factor-alpha/metabolism
Article in Chinese | WPRIM | ID: wpr-879441


OBJECTIVE@#To explore the clinical effect of the simple nucleus pulposus removal and small incision interlaminar window in the treatment of prolapsed and displaced lumbar disc herniation.@*METHODS@#From February 2016 to February 2018, 35 patients with single-segment prolapse and displaced lumbar disc herniation were treated by the simple nucleus pulposus removal and small incision interlaminar window under general anesthesia. Among them, there were 21 males and 14 females;aged (42±17) years;27 cases of L@*RESULTS@#All the operations were successful and the operation time was 30 to 60 min with an average of 40 min, the intraoperative blood loss was 10 to 30 ml with an average of 20 ml. All the patients were followed up for 1 to 3 years with an average of 1.2 years. Thirty-five patients with low back pain and lower limb symptoms were significantly relieved or disappeared. According to modified Macnab standard, 29 cases obtained excellent results, 5 good, and 1 fair.@*CONCLUSION@#Applying the concept of minimally invasive operation, small incision interlaminar window and simple nucleus pulposus removal for the treatment of prolapsed and displaced lumbar disc herniation has the advantages of short operation time, definite curative effect, and less trauma. And it is a safe and effective surgical method under the premise of strict control of the indications.

Adult , Diskectomy, Percutaneous , Endoscopy , Female , Humans , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/surgery , Male , Middle Aged , Nucleus Pulposus , Prolapse , Retrospective Studies , Treatment Outcome
Rev. colomb. reumatol ; 27(2): 120-122, ene.-jun. 2020. graf
Article in Spanish | LILACS | ID: biblio-1251645


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.

Humans , Child , Adolescent , Adult , Spine , Therapeutics , Low Back Pain , Bone and Bones , Nucleus Pulposus , Anti-Inflammatory Agents
Braz. j. med. biol. res ; 52(9): e8525, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011614


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.

Humans , Male , Female , Adult , Middle Aged , Aged , Chondrocytes/drug effects , Ginsenosides/pharmacology , Interleukin-1beta/drug effects , Interleukin-1 Receptor Accessory Protein/metabolism , Intervertebral Disc Degeneration/metabolism , Dinoprostone/metabolism , Cell Survival/drug effects , Tumor Necrosis Factor-alpha/metabolism , Low Back Pain/metabolism , Nitric Oxide Synthase/metabolism , Chondrocytes/cytology , Chondrocytes/metabolism , Ginsenosides/metabolism , Cyclooxygenase 2/metabolism , Aggrecans/metabolism , Interleukin-1beta/metabolism , Ubiquitination , Nucleus Pulposus/cytology , Nucleus Pulposus/drug effects , Nucleus Pulposus/metabolism , Inflammation/metabolism
Arq. bras. med. vet. zootec ; 68(5): 1207-1211, set.-out. 2016. ilus
Article in Portuguese | LILACS, VETINDEX | ID: biblio-827893


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)

Animals , Dogs , Intervertebral Disc/pathology , Nucleus Pulposus/pathology , Spinal Cord Injuries/veterinary , Magnetic Resonance Spectroscopy
Braz. j. med. biol. res ; 49(6): e5020, 2016. tab, graf
Article in English | LILACS | ID: biblio-951681


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.

Humans , Male , Female , Adult , Middle Aged , Aged , RNA-Binding Proteins/metabolism , MicroRNAs/metabolism , Cell Proliferation/physiology , Apoptosis Regulatory Proteins/metabolism , Nucleus Pulposus/metabolism , Reference Values , Time Factors , Apoptosis Regulatory Proteins/analysis
Chinese Medical Journal ; (24): 2338-2346, 2016.
Article in English | WPRIM | ID: wpr-307413


<p><b>BACKGROUND</b>The development of mechanically active culture systems helps increase the understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures allow for preservation of the native IVD structure, and adjacent vertebral bodies facilitate the application and control of mechanical loads. The purpose of this study was to establish loading and organ culture methods for rabbit IVD motion segments to study the effect of static load on the whole disc organ.</p><p><b>METHODS</b>IVD motion segments were harvested from rabbit lumbar spines and cultured in no-loading 6-well plates (control conditions) or custom-made apparatuses under a constant, compressive load (3 kg, 0.5 MPa) for up to 14 days. Tissue integrity, matrix synthesis, and the matrix gene expression profile were assessed after 3, 7, and 14 days of culturing and compared with those of fresh tissues.</p><p><b>RESULTS</b>The results showed that ex vivo culturing of motion segments preserved tissue integrity under no-loading conditions for 14 days whereas the static load gradually destroyed the morphology after 3 days. Proteoglycan contents were decreased under both conditions, with a more obvious decrease under static load, and proteoglycan gene expression was also downregulated. However, under static load, immunohistochemical staining intensity and collagen Type II alpha 1 (COL2A1) gene expression were significantly enhanced (61.54 ± 5.91, P = 0.035) and upregulated (1.195 ± 0.040, P = 0.000), respectively, compared with those in the controls (P < 0.05). In contrast, under constant compression, these trends were reversed. Our initial results indicated that short-term static load stimulated the synthesis of collagen Type II alpha 1; however, sustained constant compression led to progressive degeneration and specifically to a decreased proteoglycan content.</p><p><b>CONCLUSIONS</b>A loading and organ culture system for ex vivo rabbit IVD motion segments was developed. Using this system, we were able to study the effects of mechanical stimulation on the biology of IVDs, as well as the pathomechanics of IVD degeneration.</p>

Animals , Gene Expression Regulation , Immunohistochemistry , Intervertebral Disc , Metabolism , Physiology , Intervertebral Disc Degeneration , Metabolism , Male , Nucleus Pulposus , Metabolism , Physiology , Organ Culture Techniques , Methods , Rabbits , Stress, Mechanical