Intervertebral disc degeneration (IDD) is the main cause of low back pain, and little is known ab... more Intervertebral disc degeneration (IDD) is the main cause of low back pain, and little is known about its molecular and pathological mechanisms. According to reports, excessive compression is a high-risk factor for IDD; compressive stress can induce oxidative stress in nucleus pulposus (NP) cells during IDD progression that, in turn, promotes cell apoptosis and extracellular matrix (ECM) degradation. Currently, NP tissue engineering is considered a potential method for IDD treatment. However, after transplantation, NP cells may experience oxidative stress and induce apoptosis and ECM degradation due to compressive stress. Therefore, the development of strategies to protect NP cells under excessive compressive stress, including pretreatment of NP cells with antioxidants, has important clinical significance. Among the various antioxidants, bardoxolone methyl (BARD) is used to protect NP cells from damage caused by compressive stress. Our results showed that BARD can protect the viabili...
Osteoporosis can be caused by a multitude of factors and is defined by a decrease in bone density... more Osteoporosis can be caused by a multitude of factors and is defined by a decrease in bone density and mass caused by the destruction of bone microstructure, resulting in increased bone brittleness. Thus, it is a systemic bone disease in which patients are prone to fracture. The role of ferroptosis in the pathogenesis of osteoporosis has become a topic of growing interest. In this review, we discuss the cell morphology, basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, as well as the relationship between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and postmenopausal osteoporosis. Emerging biomedical research has provided new insights into the roles of ferroptosis and osteoporosis, such as in cellular function, signaling pathways, drug inhibition, and gene silencing. The pathophysiology and mechanism of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iro...
Degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degenerat... more Degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain. However, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, we first reported a comprehensive single-cell resolution transcriptional landscape of human NP. Six novel human nucleus pulposus cell (NPCs) populations were identified by distinct molecular signatures. The potential functional differences among NPC subpopulations were analyzed at the single-cell level. Predictive genes, transcriptional factors, and signal pathways with respect to degeneration grades were analyzed. We reported that fibroNPCs, one of our identified subpopulations, might be a population for NP regeneration. CD90+NPCs were observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). We unco...
Background: Percutaneous transforaminal endoscopic discectomy (PTED) is a minimally invasive surg... more Background: Percutaneous transforaminal endoscopic discectomy (PTED) is a minimally invasive surgical method for the treatment of spinal diseases. However, the operation procedure relied on the radiative interventional technology, and was conducted under local anesthesia. Method: From June 2016 to December 2019, we performed a newly developed full-endoscopic visualized foraminoplasty and discectomy under general anesthesia in 30 patients with L5/S1 LDH. In this retrospective study, the outcomes and neurological complications of this approach were evaluated. Results: The mean visual analog scale (VAS) and Oswestry Disability Index (ODI) were significantly improved after surgery. The postoperative MRI reexamination revealed that the degree of intervertebral disc degeneration of each subject was improved significantly to different degrees as compared with that before surgery. The learning curve showed operative time rapidly decreased over the earlier cases, and then tapered to a steady...
Intervertebral disk (IVD) degeneration (IVDD) can cause various spinal degenerative diseases. Cum... more Intervertebral disk (IVD) degeneration (IVDD) can cause various spinal degenerative diseases. Cumulative evidence has indicated that IVDD can result from inflammation, apoptosis, autophagy, biomechanical changes and other factors. Currently, lack of conservative treatment for degenerative spinal diseases leads to an urgent demand for clinically applicable medication to ameliorate the progression of IVDD. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol compound extracted from red wine or grapes, has shown protective effects on IVD, alleviating the progression of IVDD. Resveratrol has been demonstrated as a scavenger of free radicals both in vivo and in vitro. The antioxidant effects of resveratrol are likely attributed to its regulation on mitochondrial dysfunction or the elimination of reactive oxygen species. This review will summarize the mechanisms of the reactive oxygen species production and elaborate the mechanisms of resveratrol in retarding IVDD progression, providing a comprehensive understanding of the antioxidant effects of resveratrol in IVD.
Abstract Regulated in development and DNA damage response 1 (REDD1) is an evolutionarily conserve... more Abstract Regulated in development and DNA damage response 1 (REDD1) is an evolutionarily conserved, ubiquitous protein that responds to various cell stresses. Studies have proved REDD1 is involved in many diseases, such as osteoarthritis and cancer. The present study aimed to investigate the potential role of REDD1 in the pathogenesis of intervertebral disc degeneration (IDD). Analysis of clinical tissue samples showed REDD1 expression was up‐regulated during IDD and was correlated with the grade of disc degeneration. Overexpression of REDD1 in normal human nucleus pulposus (NP) cells resulted in extracellular matrix (ECM) degeneration. Further, we investigated the function of REDD1 using a serum deprivation‐induced IDD vitro model and found that REDD1 was up‐regulated in a temporal manner. However, hypoxia abolished this increase through down‐regulation of NF‐&kgr;B. Knockdown of REDD1 or NF‐&kgr;B by si‐RNA significantly rescued ECM from degeneration both in normoxia and hypoxia. In addition, NF‐&kgr;B/REDD1 mediated the protection of hypoxia from serum deprivation‐induced apoptosis and autophagy in NP cells. These results suggest that REDD1 might play a pivotal role in IDD pathogenesis, thereby potentially providing a new therapeutic target for IDD treatment.
Intervertebral disc (IVD) degeneration contributes largely to pathoanatomical and degenerative ch... more Intervertebral disc (IVD) degeneration contributes largely to pathoanatomical and degenerative changes of spinal structure that increase the risk of low back pain. Apoptosis in nucleus pulposus (NP) can aggravate IVD degeneration, and increasing studies have shown that interventions targeting NP cell apoptosis can ameliorate IVD degeneration, exhibiting their potential for use as therapeutic strategies. Recent data have shown that advanced glycation end products (AGEs) accumulate in NP tissues in parallel with the progression of IVD degeneration and form a microenvironment of oxidative stress. This study examined whether AGEs accumulation aggravates NP cell apoptosis and IVD degeneration, and explored the mechanisms underlying these effects. We observed that the viability and proliferation of human NP cells were significantly suppressed by AGEs treatment, mainly due to apoptosis. Furthermore, activation of the mitochondrial apoptosis pathway was detected after AGEs treatment. In add...
Spinal Giant Cell Tumors (SGCTs) are rare, aggressive, and benign tumors. Their presence in the c... more Spinal Giant Cell Tumors (SGCTs) are rare, aggressive, and benign tumors. Their presence in the cervical spine is even more exceptional. There are few reports of cervical GCT in the literature, especially recurrent cases. The treatment are challenging to clinically because radical resection is extremely difficult. In this study, we present the cases of a 25-year-old man and a 41-year-old woman who suffered from recurrent cervical GCT. They underwent extensive total spondylectomy of C3-5 and C2-4, respectively, by a combined anterior and posterior approach. Both patients had a satisfactory prognosis after 2 years followe-up, and extensive total spondylectomy provided good disease-free survival rates. Extensive total spondylectomy of cervical recurrent giant cell tumor was successfully achieved combined anterior and posterior approach. This surgical technique can be an effective option for this pathological condition, which is difficult to manage using other conventional treatment opt...
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential component of the signa... more Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential component of the signaling complex that mediates osteoclastogenesis. As an adaptor protein of E3 ligase function, TRAF6 regulates NF-κB signaling via TAK1 and I-κB kinase (IKK) activation. Here, we investigated novel mechanisms by which TRAF6 signaling is regulated under receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. A yeast two-hybrid screen system identified cellular factors that interact with TRAF6. The interactions were confirmed by glutathione S-transferase pull-down and co-immunoprecipitation assays, followed by immuno-blotting. The role of TRAF6 in bone growth and remodeling was determined by osteoclast differentiation and bone-resorption pit assays. Regulatory mechanisms were examined by co-immunoprecipitation, immuno-blotting, real-time polymerase chain reaction, and luciferase reporter assays. We show that B-cell chronic lymphatic leukemia protein 3 (BCL3) interac...
Autophagy dysfunction has been observed in intervertebral disc degeneration (IVDD) cells, a main ... more Autophagy dysfunction has been observed in intervertebral disc degeneration (IVDD) cells, a main contributing factor to cell death, but the precise role of autophagy during IVDD is still controversial. This study aimed to investigate the role of autophagy involved in the pathogenesis of human IVDD and determine the signal transduction pathways responsible for compression-induced autophagy in human nucleus pulposus (NP) cells. Autophagy, suppressing the induction of apoptosis, was activated in NP cells exposed to compression. Molecular analysis showed that compression promoted the activity of NRF1, a transcription regulator increasing Atg7 expression by binding to its promoter, through activating the Ras/MEK/ERK signaling in NP cells. Loss- and gain-of-function studies demonstrate that NRF1 induced autophagy and dampened the apoptotic response by promoting Atg7 expression in NP cells subjected to compression. This study confirmed that compression-induced autophagy could be induced by...
The aim of the study was to evaluate the safety and short-term effects of dynamic stabilization v... more The aim of the study was to evaluate the safety and short-term effects of dynamic stabilization via minimally invasive system for degenerative lumbar spinal stenosis. Patients with degenerative lumbar spinal stenosis and treated with Transforaminal Lumbar Interbody Fusion via minimally invasive minimally system (mis-TLIF) were served as the control group.From April 2011 to March 2015, 47 patients (29 male, 18 female; mean age 47.6 [range, 26-52] years) with lumbar spinal stenosis were treated with decompression and excision of herniated disk via the minimally invasive system combined with the dynamic fixation technique, and 42 patients as control group with mis-TLIF. Minimally invasive surgeries were performed via the posterior incision approach. The clinical outcomes were evaluated by comparing the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) scores, and the ROMs of the adjacent segment before and after surgery. The postoperative complications related to the imp...
The purpose of this retrospective study was to investigate the clinical outcomes of full-endoscop... more The purpose of this retrospective study was to investigate the clinical outcomes of full-endoscopic discectomy via the interlaminar approach in the treatment of lumbar disc herniation (LDH) at L4-L5 under general anesthesia.Eighty-four patients who underwent full-endoscopic discectomy via the interlaminar approach at L4-L5 or L5-S1 were included. Durations of surgery, intraoperative radiation, postoperative bedrest, and hospitalization as well as perioperative complications were recorded. The visual analog scale (VAS) score for leg and back pain and the Oswestry disability index (ODI) score were evaluated preoperatively and at 3, 6, and 12 months postoperatively.The mean durations of surgeries in surgeries involving L4-L5 and L5-S1 were 69.8 ± 18.8 and 67.0 ± 20.1 minutes, respectively. The mean durations of intraoperative radiation were 1.2 ± 0.3 and 1.3 ± 0.3 seconds, respectively. The mean VAS and ODI scores improved significantly postoperatively compared with the preoperative sc...
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018
Intervertebral disc degeneration (IDD) is a pathological process that is the primary cause of low... more Intervertebral disc degeneration (IDD) is a pathological process that is the primary cause of low back pain and is potentially mediated by compromised stress defense. Sestrins (Sesn) promote cell survival under stress conditions and regulate AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signaling. Here, we investigated the expression of Sesn in normal and degraded nucleus pulposus (NP) cells and its potential roles during IDD pathogenesis. Sesn expression in normal and degraded NP cells was determined by quantitative polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. Sesn function was investigated by using Sesn knockdown and overexpression techniques with analysis of extracellular matrix (ECM), cell apoptosis, autophagy, AMPK, and mTOR activation. In human cultured NP cells, Sesn expression was significantly decreased in degraded NP cells at both the RNA and protein levels. The expression of Sesn1, 2, and 3 increased a...
International journal of molecular medicine, Jan 19, 2018
In contrast to healthy intervertebral discs (IVDs), degenerate IVDs become vascularized. Here, we... more In contrast to healthy intervertebral discs (IVDs), degenerate IVDs become vascularized. Here, we determined the role of an angiogenesis promoter, angiopoietin (Ang)-2, in the pathology of IVD degeneration (IDD). We evaluated degree of IDD using the Pfirrmann grading system. We used quantitative real-time polymerase chain reaction and western blotting to analyze ANG2 gene expression and Ang-2 protein levels, respectively. The involvement of Ang-2 in IVD degradation and regulation of nuclear factor-κB (NF-κB) signaling was examined by immunohistochemistry, western blotting and immunofluorescence. As a result, 10 samples with grades II and III IDD were categorized as the mild IDD group; for comparison, another 10 specimens with grades IV and V constituted the severe IDD group. Ang-2 expression was significantly higher in severe IDD than in mild IDD. Exogenous Ang-2 administration led to increased production of catabolic proteinases and loss of aggrecan and collagen II in degenerative ...
Clinical and experimental immunology, Jan 30, 2017
Farnesyltransferase inhibitors have been tested in clinical trials for the treatment of tumours. ... more Farnesyltransferase inhibitors have been tested in clinical trials for the treatment of tumours. In sepsis, the binding of programmed death 1 (PD-1) to programmed death ligand 1 (PD-L1) promotes lymphocyte apoptosis and decreases cytokine expression, thus affecting survival rates. The PD-1/PD-L1 pathway plays an important role in chronic viral infection, bacterial infection and sepsis. However, the precise immunosuppressive and anti-inflammatory functions of this pathway remain poorly understood. In our previous study, the induction of sepsis by caecal ligation and puncture (CLP) resulted in increased farnesyltransferase activity and farnesylated protein levels in the spleen relative to sham treatment. However, the effect of inhibition of farnesyltransferase activity on overall survival rates in patients with sepsis and the specific signalling pathway involved remain to be investigated. In this study, mice with CLP-induced sepsis were treated with farnesyltransferase inhibitor (FTI-...
Low back pain is a common problem, mainly caused by intervertebral disc degeneration (IDD). An im... more Low back pain is a common problem, mainly caused by intervertebral disc degeneration (IDD). An important pathophysiological characteristic of IDD is the loss of homeostatic balance of the extracellular matrix metabolism. Interleukin-1β (IL-1β) is one of the inflammatory mediators stimulating the degradation of extracellular matrix in the nucleus pulposus (NP) and contributing to IDD pathogenesis. Icariin, which is isolated from Epimedium brevicornum, acts as an anti-inflammatory drug. This study aimed to explore the pharmacological effects of icariin in IDD by simulating NP inflammation in vitro. Human NP cells were isolated and cultured in vitro. NP cells were pretreated with icariin (0.1, 1 and 10 μM) and stimulated by IL-1β (10 ng/ml). The concentration of Prostaglandin E2 was determined by enzyme-linked immunosorbent assay. Nitric oxide was determined by Griess reagent assay. The expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), degrading enzymes, c...
Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of ex... more Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression i...
This study investigated the expression and function of the microRNA-494 in intervertebral disc de... more This study investigated the expression and function of the microRNA-494 in intervertebral disc degeneration (IDD). MicroRNA-494 expression was upregulated during IDD progression; its overexpression increased the expression of ECM catabolic factors such as matrix metalloproteinase and A disintegrin and metalloproteinase with thrombospondin motif in NP cells while decreasing that of anabolic genes such as type II collagen and aggrecan; it also induced the apoptosis of NP cells, as determined by flow cytometry. These effects were reversed by microRNA-494 inhibitor treatment. SOX9 was identified as a target of negative regulation by microRNA-494. Promoter hypomethylation and NF-κB activation were associated with microRNA-494 upregulation in IDD. MicroRNA-494 expression in degenerative nucleus pulposus (NP) tissue was assessed by quantitative real-time PCR. The effect of microRNA-494 on extracellular matrix (ECM) metabolism and NP cell apoptosis was evaluated by transfection of microRNA-...
Laboratory investigation; a journal of technical methods and pathology, Aug 10, 2017
Although evidence shows that intervertebral disc degeneration is generally characterized by angio... more Although evidence shows that intervertebral disc degeneration is generally characterized by angiogenesis, the role of angiopoietin has not been investigated. This study examined the presence of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) within the native intervertebral disc (IVD) and elucidated their functions in the regulation of nucleus pulposus (NP) cells. Initial investigation of uncultured NP tissue revealed that Ang-1 and Ang-2 were expressed by native NP cells. Ang-2 expression was significantly increased in infiltrated and degenerate samples relative to normal samples. The ratio of Ang-2/Ang-1 in tissues from patients increased markedly with increasing age and level of degeneration of the IVD. The ratio of both Ang-2/Ang-1 mRNA and protein increased over time when cells were subjected to constant pressure at 1 Mpa in vitro. Our findings indicate that Ang-2 plays a role in suppressing cell adhesion and viability, and promotes the apoptosis of NP cells and that Ang-2 ca...
Clinical science (London, England : 1979), Jan 24, 2017
Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneratio... more Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration. However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, that was transcribed in the opposite direction of ADAMTS5. In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation, in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to i...
Intervertebral disc degeneration (IDD) is the main cause of low back pain, and little is known ab... more Intervertebral disc degeneration (IDD) is the main cause of low back pain, and little is known about its molecular and pathological mechanisms. According to reports, excessive compression is a high-risk factor for IDD; compressive stress can induce oxidative stress in nucleus pulposus (NP) cells during IDD progression that, in turn, promotes cell apoptosis and extracellular matrix (ECM) degradation. Currently, NP tissue engineering is considered a potential method for IDD treatment. However, after transplantation, NP cells may experience oxidative stress and induce apoptosis and ECM degradation due to compressive stress. Therefore, the development of strategies to protect NP cells under excessive compressive stress, including pretreatment of NP cells with antioxidants, has important clinical significance. Among the various antioxidants, bardoxolone methyl (BARD) is used to protect NP cells from damage caused by compressive stress. Our results showed that BARD can protect the viabili...
Osteoporosis can be caused by a multitude of factors and is defined by a decrease in bone density... more Osteoporosis can be caused by a multitude of factors and is defined by a decrease in bone density and mass caused by the destruction of bone microstructure, resulting in increased bone brittleness. Thus, it is a systemic bone disease in which patients are prone to fracture. The role of ferroptosis in the pathogenesis of osteoporosis has become a topic of growing interest. In this review, we discuss the cell morphology, basic mechanisms of ferroptosis, the relationship between ferroptosis and osteoclasts and osteoblasts, as well as the relationship between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and postmenopausal osteoporosis. Emerging biomedical research has provided new insights into the roles of ferroptosis and osteoporosis, such as in cellular function, signaling pathways, drug inhibition, and gene silencing. The pathophysiology and mechanism of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iro...
Degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degenerat... more Degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain. However, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, we first reported a comprehensive single-cell resolution transcriptional landscape of human NP. Six novel human nucleus pulposus cell (NPCs) populations were identified by distinct molecular signatures. The potential functional differences among NPC subpopulations were analyzed at the single-cell level. Predictive genes, transcriptional factors, and signal pathways with respect to degeneration grades were analyzed. We reported that fibroNPCs, one of our identified subpopulations, might be a population for NP regeneration. CD90+NPCs were observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). We unco...
Background: Percutaneous transforaminal endoscopic discectomy (PTED) is a minimally invasive surg... more Background: Percutaneous transforaminal endoscopic discectomy (PTED) is a minimally invasive surgical method for the treatment of spinal diseases. However, the operation procedure relied on the radiative interventional technology, and was conducted under local anesthesia. Method: From June 2016 to December 2019, we performed a newly developed full-endoscopic visualized foraminoplasty and discectomy under general anesthesia in 30 patients with L5/S1 LDH. In this retrospective study, the outcomes and neurological complications of this approach were evaluated. Results: The mean visual analog scale (VAS) and Oswestry Disability Index (ODI) were significantly improved after surgery. The postoperative MRI reexamination revealed that the degree of intervertebral disc degeneration of each subject was improved significantly to different degrees as compared with that before surgery. The learning curve showed operative time rapidly decreased over the earlier cases, and then tapered to a steady...
Intervertebral disk (IVD) degeneration (IVDD) can cause various spinal degenerative diseases. Cum... more Intervertebral disk (IVD) degeneration (IVDD) can cause various spinal degenerative diseases. Cumulative evidence has indicated that IVDD can result from inflammation, apoptosis, autophagy, biomechanical changes and other factors. Currently, lack of conservative treatment for degenerative spinal diseases leads to an urgent demand for clinically applicable medication to ameliorate the progression of IVDD. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol compound extracted from red wine or grapes, has shown protective effects on IVD, alleviating the progression of IVDD. Resveratrol has been demonstrated as a scavenger of free radicals both in vivo and in vitro. The antioxidant effects of resveratrol are likely attributed to its regulation on mitochondrial dysfunction or the elimination of reactive oxygen species. This review will summarize the mechanisms of the reactive oxygen species production and elaborate the mechanisms of resveratrol in retarding IVDD progression, providing a comprehensive understanding of the antioxidant effects of resveratrol in IVD.
Abstract Regulated in development and DNA damage response 1 (REDD1) is an evolutionarily conserve... more Abstract Regulated in development and DNA damage response 1 (REDD1) is an evolutionarily conserved, ubiquitous protein that responds to various cell stresses. Studies have proved REDD1 is involved in many diseases, such as osteoarthritis and cancer. The present study aimed to investigate the potential role of REDD1 in the pathogenesis of intervertebral disc degeneration (IDD). Analysis of clinical tissue samples showed REDD1 expression was up‐regulated during IDD and was correlated with the grade of disc degeneration. Overexpression of REDD1 in normal human nucleus pulposus (NP) cells resulted in extracellular matrix (ECM) degeneration. Further, we investigated the function of REDD1 using a serum deprivation‐induced IDD vitro model and found that REDD1 was up‐regulated in a temporal manner. However, hypoxia abolished this increase through down‐regulation of NF‐&kgr;B. Knockdown of REDD1 or NF‐&kgr;B by si‐RNA significantly rescued ECM from degeneration both in normoxia and hypoxia. In addition, NF‐&kgr;B/REDD1 mediated the protection of hypoxia from serum deprivation‐induced apoptosis and autophagy in NP cells. These results suggest that REDD1 might play a pivotal role in IDD pathogenesis, thereby potentially providing a new therapeutic target for IDD treatment.
Intervertebral disc (IVD) degeneration contributes largely to pathoanatomical and degenerative ch... more Intervertebral disc (IVD) degeneration contributes largely to pathoanatomical and degenerative changes of spinal structure that increase the risk of low back pain. Apoptosis in nucleus pulposus (NP) can aggravate IVD degeneration, and increasing studies have shown that interventions targeting NP cell apoptosis can ameliorate IVD degeneration, exhibiting their potential for use as therapeutic strategies. Recent data have shown that advanced glycation end products (AGEs) accumulate in NP tissues in parallel with the progression of IVD degeneration and form a microenvironment of oxidative stress. This study examined whether AGEs accumulation aggravates NP cell apoptosis and IVD degeneration, and explored the mechanisms underlying these effects. We observed that the viability and proliferation of human NP cells were significantly suppressed by AGEs treatment, mainly due to apoptosis. Furthermore, activation of the mitochondrial apoptosis pathway was detected after AGEs treatment. In add...
Spinal Giant Cell Tumors (SGCTs) are rare, aggressive, and benign tumors. Their presence in the c... more Spinal Giant Cell Tumors (SGCTs) are rare, aggressive, and benign tumors. Their presence in the cervical spine is even more exceptional. There are few reports of cervical GCT in the literature, especially recurrent cases. The treatment are challenging to clinically because radical resection is extremely difficult. In this study, we present the cases of a 25-year-old man and a 41-year-old woman who suffered from recurrent cervical GCT. They underwent extensive total spondylectomy of C3-5 and C2-4, respectively, by a combined anterior and posterior approach. Both patients had a satisfactory prognosis after 2 years followe-up, and extensive total spondylectomy provided good disease-free survival rates. Extensive total spondylectomy of cervical recurrent giant cell tumor was successfully achieved combined anterior and posterior approach. This surgical technique can be an effective option for this pathological condition, which is difficult to manage using other conventional treatment opt...
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential component of the signa... more Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential component of the signaling complex that mediates osteoclastogenesis. As an adaptor protein of E3 ligase function, TRAF6 regulates NF-κB signaling via TAK1 and I-κB kinase (IKK) activation. Here, we investigated novel mechanisms by which TRAF6 signaling is regulated under receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. A yeast two-hybrid screen system identified cellular factors that interact with TRAF6. The interactions were confirmed by glutathione S-transferase pull-down and co-immunoprecipitation assays, followed by immuno-blotting. The role of TRAF6 in bone growth and remodeling was determined by osteoclast differentiation and bone-resorption pit assays. Regulatory mechanisms were examined by co-immunoprecipitation, immuno-blotting, real-time polymerase chain reaction, and luciferase reporter assays. We show that B-cell chronic lymphatic leukemia protein 3 (BCL3) interac...
Autophagy dysfunction has been observed in intervertebral disc degeneration (IVDD) cells, a main ... more Autophagy dysfunction has been observed in intervertebral disc degeneration (IVDD) cells, a main contributing factor to cell death, but the precise role of autophagy during IVDD is still controversial. This study aimed to investigate the role of autophagy involved in the pathogenesis of human IVDD and determine the signal transduction pathways responsible for compression-induced autophagy in human nucleus pulposus (NP) cells. Autophagy, suppressing the induction of apoptosis, was activated in NP cells exposed to compression. Molecular analysis showed that compression promoted the activity of NRF1, a transcription regulator increasing Atg7 expression by binding to its promoter, through activating the Ras/MEK/ERK signaling in NP cells. Loss- and gain-of-function studies demonstrate that NRF1 induced autophagy and dampened the apoptotic response by promoting Atg7 expression in NP cells subjected to compression. This study confirmed that compression-induced autophagy could be induced by...
The aim of the study was to evaluate the safety and short-term effects of dynamic stabilization v... more The aim of the study was to evaluate the safety and short-term effects of dynamic stabilization via minimally invasive system for degenerative lumbar spinal stenosis. Patients with degenerative lumbar spinal stenosis and treated with Transforaminal Lumbar Interbody Fusion via minimally invasive minimally system (mis-TLIF) were served as the control group.From April 2011 to March 2015, 47 patients (29 male, 18 female; mean age 47.6 [range, 26-52] years) with lumbar spinal stenosis were treated with decompression and excision of herniated disk via the minimally invasive system combined with the dynamic fixation technique, and 42 patients as control group with mis-TLIF. Minimally invasive surgeries were performed via the posterior incision approach. The clinical outcomes were evaluated by comparing the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) scores, and the ROMs of the adjacent segment before and after surgery. The postoperative complications related to the imp...
The purpose of this retrospective study was to investigate the clinical outcomes of full-endoscop... more The purpose of this retrospective study was to investigate the clinical outcomes of full-endoscopic discectomy via the interlaminar approach in the treatment of lumbar disc herniation (LDH) at L4-L5 under general anesthesia.Eighty-four patients who underwent full-endoscopic discectomy via the interlaminar approach at L4-L5 or L5-S1 were included. Durations of surgery, intraoperative radiation, postoperative bedrest, and hospitalization as well as perioperative complications were recorded. The visual analog scale (VAS) score for leg and back pain and the Oswestry disability index (ODI) score were evaluated preoperatively and at 3, 6, and 12 months postoperatively.The mean durations of surgeries in surgeries involving L4-L5 and L5-S1 were 69.8 ± 18.8 and 67.0 ± 20.1 minutes, respectively. The mean durations of intraoperative radiation were 1.2 ± 0.3 and 1.3 ± 0.3 seconds, respectively. The mean VAS and ODI scores improved significantly postoperatively compared with the preoperative sc...
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018
Intervertebral disc degeneration (IDD) is a pathological process that is the primary cause of low... more Intervertebral disc degeneration (IDD) is a pathological process that is the primary cause of low back pain and is potentially mediated by compromised stress defense. Sestrins (Sesn) promote cell survival under stress conditions and regulate AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signaling. Here, we investigated the expression of Sesn in normal and degraded nucleus pulposus (NP) cells and its potential roles during IDD pathogenesis. Sesn expression in normal and degraded NP cells was determined by quantitative polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. Sesn function was investigated by using Sesn knockdown and overexpression techniques with analysis of extracellular matrix (ECM), cell apoptosis, autophagy, AMPK, and mTOR activation. In human cultured NP cells, Sesn expression was significantly decreased in degraded NP cells at both the RNA and protein levels. The expression of Sesn1, 2, and 3 increased a...
International journal of molecular medicine, Jan 19, 2018
In contrast to healthy intervertebral discs (IVDs), degenerate IVDs become vascularized. Here, we... more In contrast to healthy intervertebral discs (IVDs), degenerate IVDs become vascularized. Here, we determined the role of an angiogenesis promoter, angiopoietin (Ang)-2, in the pathology of IVD degeneration (IDD). We evaluated degree of IDD using the Pfirrmann grading system. We used quantitative real-time polymerase chain reaction and western blotting to analyze ANG2 gene expression and Ang-2 protein levels, respectively. The involvement of Ang-2 in IVD degradation and regulation of nuclear factor-κB (NF-κB) signaling was examined by immunohistochemistry, western blotting and immunofluorescence. As a result, 10 samples with grades II and III IDD were categorized as the mild IDD group; for comparison, another 10 specimens with grades IV and V constituted the severe IDD group. Ang-2 expression was significantly higher in severe IDD than in mild IDD. Exogenous Ang-2 administration led to increased production of catabolic proteinases and loss of aggrecan and collagen II in degenerative ...
Clinical and experimental immunology, Jan 30, 2017
Farnesyltransferase inhibitors have been tested in clinical trials for the treatment of tumours. ... more Farnesyltransferase inhibitors have been tested in clinical trials for the treatment of tumours. In sepsis, the binding of programmed death 1 (PD-1) to programmed death ligand 1 (PD-L1) promotes lymphocyte apoptosis and decreases cytokine expression, thus affecting survival rates. The PD-1/PD-L1 pathway plays an important role in chronic viral infection, bacterial infection and sepsis. However, the precise immunosuppressive and anti-inflammatory functions of this pathway remain poorly understood. In our previous study, the induction of sepsis by caecal ligation and puncture (CLP) resulted in increased farnesyltransferase activity and farnesylated protein levels in the spleen relative to sham treatment. However, the effect of inhibition of farnesyltransferase activity on overall survival rates in patients with sepsis and the specific signalling pathway involved remain to be investigated. In this study, mice with CLP-induced sepsis were treated with farnesyltransferase inhibitor (FTI-...
Low back pain is a common problem, mainly caused by intervertebral disc degeneration (IDD). An im... more Low back pain is a common problem, mainly caused by intervertebral disc degeneration (IDD). An important pathophysiological characteristic of IDD is the loss of homeostatic balance of the extracellular matrix metabolism. Interleukin-1β (IL-1β) is one of the inflammatory mediators stimulating the degradation of extracellular matrix in the nucleus pulposus (NP) and contributing to IDD pathogenesis. Icariin, which is isolated from Epimedium brevicornum, acts as an anti-inflammatory drug. This study aimed to explore the pharmacological effects of icariin in IDD by simulating NP inflammation in vitro. Human NP cells were isolated and cultured in vitro. NP cells were pretreated with icariin (0.1, 1 and 10 μM) and stimulated by IL-1β (10 ng/ml). The concentration of Prostaglandin E2 was determined by enzyme-linked immunosorbent assay. Nitric oxide was determined by Griess reagent assay. The expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), degrading enzymes, c...
Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of ex... more Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression i...
This study investigated the expression and function of the microRNA-494 in intervertebral disc de... more This study investigated the expression and function of the microRNA-494 in intervertebral disc degeneration (IDD). MicroRNA-494 expression was upregulated during IDD progression; its overexpression increased the expression of ECM catabolic factors such as matrix metalloproteinase and A disintegrin and metalloproteinase with thrombospondin motif in NP cells while decreasing that of anabolic genes such as type II collagen and aggrecan; it also induced the apoptosis of NP cells, as determined by flow cytometry. These effects were reversed by microRNA-494 inhibitor treatment. SOX9 was identified as a target of negative regulation by microRNA-494. Promoter hypomethylation and NF-κB activation were associated with microRNA-494 upregulation in IDD. MicroRNA-494 expression in degenerative nucleus pulposus (NP) tissue was assessed by quantitative real-time PCR. The effect of microRNA-494 on extracellular matrix (ECM) metabolism and NP cell apoptosis was evaluated by transfection of microRNA-...
Laboratory investigation; a journal of technical methods and pathology, Aug 10, 2017
Although evidence shows that intervertebral disc degeneration is generally characterized by angio... more Although evidence shows that intervertebral disc degeneration is generally characterized by angiogenesis, the role of angiopoietin has not been investigated. This study examined the presence of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) within the native intervertebral disc (IVD) and elucidated their functions in the regulation of nucleus pulposus (NP) cells. Initial investigation of uncultured NP tissue revealed that Ang-1 and Ang-2 were expressed by native NP cells. Ang-2 expression was significantly increased in infiltrated and degenerate samples relative to normal samples. The ratio of Ang-2/Ang-1 in tissues from patients increased markedly with increasing age and level of degeneration of the IVD. The ratio of both Ang-2/Ang-1 mRNA and protein increased over time when cells were subjected to constant pressure at 1 Mpa in vitro. Our findings indicate that Ang-2 plays a role in suppressing cell adhesion and viability, and promotes the apoptosis of NP cells and that Ang-2 ca...
Clinical science (London, England : 1979), Jan 24, 2017
Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneratio... more Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration. However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, that was transcribed in the opposite direction of ADAMTS5. In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation, in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to i...
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