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1.
In Vitro Cell Dev Biol Anim ; 60(3): 287-299, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38485818

ABSTRACT

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1ß-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1ß, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1ß to simulate IVDD environment and divided into the control group, IL-1ß group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway-related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1ß, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1ß-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1ß-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.


Subject(s)
Ginsenosides , Intervertebral Disc Degeneration , Intervertebral Disc , Nucleus Pulposus , Animals , Rats , Aggrecans/genetics , Apoptosis , Collagen/pharmacology , Inflammation/pathology , Interleukin-6/metabolism , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/drug therapy , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Matrix Metalloproteinase 3/metabolism , NF-kappa B/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism
2.
Am J Pathol ; 194(2): 280-295, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37981220

ABSTRACT

In this study, knockout of FOXO3 was found to impair intervertebral disc maturation and homeostasis in postnatal mice as well as facilitating extracellular matrix degradation. RNA sequencing can uncover disease-related gene expression and investigate disease pathophysiology. High-throughput transcriptome sequencing and experimental validations were used to identify the essential gene and mechanism involved in intervertebral disc degeneration (IDD). Nucleus pulposus (NP) tissue samples were collected from the mice with conditional knockout of FOXO3 (FOXO3 KO) for high-throughput sequencing, followed by screening of differentially expressed lncRNAs and mRNAs. The mRNAs were subjected to GO and KEGG enrichment analyses. Interactions among FOXO3, HOTTIP, miR-615-3p, and COL2A1 were analyzed. NP cells were subjected to a series of mimics, inhibitors, overexpression plasmids, and shRNAs to validate the mechanisms of FOXO3 in controlling HOTTIP/miR-615-3p/COL2A1 in IDD. Mechanistically, FOXO3 transcriptionally activated HOTTIP, facilitated the competitive HOTTIP binding to miR-615-3p, and increased the expression of the miR-615-3p target gene COL2A1. Thus, NP cell proliferation was induced, cell apoptosis was diminished, resulting in delayed development of IDD. Based on these data, the transcription factor FOXO3 may decrease miR-615-3p binding to COL2A1 and up-regulate COL2A1 expression by activating HOTTIP transcription, which in turn inhibits NP cell apoptosis and promotes its proliferation, to prevent the degradation of intervertebral disc matrix and maintain the normal physiological function of intervertebral disc, thereby preventing the occurrence and development of IDD.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , MicroRNAs , Nucleus Pulposus , Mice , Animals , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Expression Regulation , Nucleus Pulposus/metabolism , RNA, Messenger/metabolism , Apoptosis/genetics
3.
Exp Cell Res ; 430(1): 113699, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37364764

ABSTRACT

Excessive apoptosis of nucleus pulposus (NP) cells is the main pathological change in intervertebral disc degeneration (IVDD) progression. Pleomorphic adenoma gene like-2 (PLAGL2) plays a key role in cell apoptosis, however, the effect of PLAGL2 on IVDD has not been clarified yet. In this study, we established mouse IVDD models via the annulus fibrosis needle puncture, TUNEL and safranin O staining were used to verify the successful establishment of IVDD models, and PLAGL2 expression was detected in disc tissues. Then, NP cells isolated from disc tissues were used to construct PLAGL2 knockdown cells. PLAGL2 expression in NP cells was analyzed with qRT-PCR and Western blot. The impact of PLAGL2 on the viability, apoptosis, and mitochondria function of NP cells was evaluated by MTT assay, TUNEL, JC1 staining, and flow cytometry assay. Additionally, the regulatory mechanism of PLAGL2 was further assessed. We found that PLAGL2 was upregulated in IVDD disc tissues and serum deprivation (SD)-stimulated NP cells. PLAGL2 knockdown inhibited apoptosis and mitochondria damage in NP cells. Moreover, knockdown of PLAGL2 downregulated the expression of downstream apoptosis-related factors RASSF5, Nip3, and p73. Mechanically, PLAGL2 transcriptionally activated RASSF5 via binding to its promoter. In general, our findings indicate that PLAGL2 induces apoptosis in NP cells and aggravates IVDD progression. This study provides a promising therapeutic target for IVDD treatment.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Nucleus Pulposus , Animals , Mice , Rats , Apoptosis , Genes, Tumor Suppressor , Intervertebral Disc/metabolism , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Nucleus Pulposus/metabolism , Rats, Sprague-Dawley , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism
4.
Aging Cell ; 21(8): e13677, 2022 08.
Article in English | MEDLINE | ID: mdl-35907249

ABSTRACT

The transcription factor p300 is reportedly involved in age-associated human diseases, including intervertebral disc degeneration (IDD). In this study, we investigate the potential role and pathophysiological mechanism of p300 in IDD. Clinical tissue samples were collected from patients with lumbar disc herniation (LDH), in which the expression of p300, forkhead box O3 (FOXO3), and sirtuin 1 (Sirt1) was determined. Nucleus pulposus cells (NPCs) isolated from clinical degenerative intervertebral disc (IVD) tissues were introduced with oe-p300, oe-FOXO3, Wnt/ß-catenin agonist 1, C646 (p300/CBP inhibitor), or si-p300 to explore the functional role of p300 in IDD and to characterize the relationship between p300 and the FOXO3/Sirt1/Wnt/ß-catenin pathway. Also, we established a rat IDD model by inducing needle puncture injuries in the caudal IVDs for further verification of p300 functional role. We found that p300 was downregulated in the clinical tissues and NPCs of IDD. Overexpression of p300 promoted the proliferation and autophagy of NPCs while inhibiting cell apoptosis, which was associated with FOXO3 upregulation. p300 could increase the expression of FOXO3 by binding to the Sirt1 promoter, and thus, contributed to inactivation of the Wnt/ß-catenin pathway. In vivo results further displayed that p300 slowed down the progression of IDD by disrupting the Wnt/ß-catenin pathway through the FOXO3/Sirt1 axis. Taken together, we suggest that p300 can act to suppress IDD via a FOXO3-dependent mechanism, highlighting a potential novel target for treatment of IDD.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Nucleus Pulposus , Animals , Apoptosis , Forkhead Box Protein O3/genetics , Forkhead Box Protein O3/metabolism , Humans , Intervertebral Disc/metabolism , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Nucleus Pulposus/metabolism , Rats , Sirtuin 1/genetics , Sirtuin 1/metabolism , Wnt Signaling Pathway , beta Catenin/metabolism
5.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(1): 71-78, 2022 Jan 15.
Article in Chinese | MEDLINE | ID: mdl-35038802

ABSTRACT

OBJECTIVE: To compare the effectiveness of percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) and Wiltse-approach TLIF (W-TLIF) in the treatment of lumbar spondylolisthesis. METHODS: The clinical data of 47 patients with lumbar spondylolisthesis who met the selection criteria between July 2018 and June 2019 were retrospectively analyzed, in which 21 patients were treated with PE-TLIF (PE-TLIF group) and 26 patients were treated with W-TLIF (W-TLIF group). There was no significant difference between the two groups in age, gender, disease duration, level of spondylolisthesis vertebrae, spondylolisthesis degree, spondylolisthesis type, and preoperative visual analogue scale (VAS) score of low back pain and leg pain, lumbar Japanese Orthopaedic Association (JOA) score, and the disc height (DH), segmental lordosis (SL), and Taillard index (TI) of the operated vertebrae ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage, postoperative bedridden time, and complications were compared between the two groups. The VAS score and JOA score were used to evaluate the improvement of pain and function. At last follow-up, DH, SL, and TI of operated vertebrae were measured by X-ray films, and lumbar CT was performed to evaluate the interbody fusion. RESULTS: Compared with W-TLIF group, the operation time in PE-TLIF group was significantly longer, but the intraoperative blood loss and postoperative drainage were significantly less, and the postoperative bedridden time was significantly shorter ( P<0.05). There were 2 cases of transient lower limb radiating pain in PE-TLIF group and 1 case of superficial incision infection in W-TLIF group. There was no significant difference in the incidence of complications (9.5% vs. 3.8%) between the two groups ( χ 2=0.037, P=0.848). The patients in both groups were followed up 12-24 months, with an average of 17.3 months in PE-TLIF group and 17.7 months in W-TLIF group. The VAS scores of low back pain and leg pain, and the JOA scores of the two groups significantly improved at each time point after operation when compared with those before operation ( P<0.05). Compared with W-TLIF group, the VAS scores of low back pain in PE-TLIF group significantly lower at 3 days and 3 months after operation ( P<0.05), and the JOA score of PE-TLIF group was significantly higher at 3 months after operation ( P<0.05), and there was no significant difference in each score at any other time point between the two groups ( P>0.05). At last follow-up, the DH, SL, and TI of operated vertebrae of the two groups significantly improved when compared with those before operation ( P<0.05), and there was no significant difference in the differences of each parameter between the two groups ( P>0.05). According to Suk's standard, the fusion rates of PE-TLIF group and W-TLIF group were 90.5% (19/21) and 92.3% (24/26), respectively, with no significant difference ( χ 2=0.000, P=1.000). At last follow-up, there was no case of Cage sunk into the adjacent vertebral body, or dislodgement of Cage anteriorly or posteriorly in both groups. CONCLUSION: PE-TLIF and W-TLIF are both effective in the treatment of grade Ⅰ and Ⅱ lumbar spondylolisthesis. Although the operation time is prolonged, PE-TLIF has less intraoperative blood loss and postoperative drainage, shorter postoperative bedridden time, and can get more obvious short-term improvement of low back pain and function.


Subject(s)
Spinal Fusion , Spondylolisthesis , Animals , Humans , Lumbar Vertebrae/surgery , Lumbosacral Region , Minimally Invasive Surgical Procedures , Retrospective Studies , Spondylolisthesis/surgery , Treatment Outcome
6.
Medicine (Baltimore) ; 100(23): e26021, 2021 Jun 11.
Article in English | MEDLINE | ID: mdl-34114989

ABSTRACT

ABSTRACT: The present study aimed to develop nomograms to predict survival in patients with chondroblastic osteosarcoma (COS).An analysis was conducted of 320 cases of COS collected from the surveillance, epidemiology, and end results (SEER) database between 2004 and 2015. Independent prognostic factors were screened using univariate and multivariate Cox analyses. Subsequently, nomograms were established to predict the patients' cancer-specific survival (CSS) and overall survival (OS) rates. The prediction accuracy and discriminative ability of the nomograms were examined using calibration curves and the concordance index (C-index).As revealed in the univariate and multivariate Cox regression analysis, age, tumor size, the primary site, the presence of metastasis, a history of having undergone surgery, and a history of having received radiotherapy were found to be independent prognostic factors associated with survival in patients with COS (all P < .05). Furthermore, age >39 years, the presence of distant metastasis, no history of having undergone any surgery, and tumor size >103 mm were found to be associated with poor prognosis in patients, while the primary site of the mandible and no history of having undergone radiotherapy showed associations with a more favorable prognosis in patients. Next, nomograms were constructed to predict the OS and CSS in patients with COS.We constructed nomograms that can provide accurate survival predictions in patients with chondroblastic osteosarcoma. These nomograms can help surgeons customize the treatment strategies for patients with chondroblastic osteosarcoma.


Subject(s)
Chondroblastoma , Nomograms , Osteosarcoma , Risk Adjustment/methods , SEER Program/statistics & numerical data , Age Factors , Chondroblastoma/mortality , Chondroblastoma/pathology , Chondroblastoma/therapy , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Osteosarcoma/mortality , Osteosarcoma/pathology , Osteosarcoma/therapy , Predictive Value of Tests , Prognosis , Radiotherapy/methods , Radiotherapy/statistics & numerical data , Surgical Procedures, Operative/methods , Surgical Procedures, Operative/statistics & numerical data , Survival Analysis , Tumor Burden
7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(6): 761-768, 2020 Jun 15.
Article in Chinese | MEDLINE | ID: mdl-32538569

ABSTRACT

OBJECTIVE: To compare the clinical and radiological effectiveness of oblique lumbar interbody fusion (OLIF) and posterior lumbar interbody fusion (PLIF) in the treatment of Cage dislodgement after lumbar surgery. METHODS: The clinical data of 40 patients who underwent revision surgery due to Cage dislodgement after lumbar surgery betweem April 2013 and March 2017 were retrospectively analyzed. Among them, 18 patients underwent OLIF (OLIF group) and 22 patients underwent PLIF (PLIF group) for revision. There was no significant difference between the two groups in age, gender, body mass index, intervals between primary surgery and revision surgery, number of primary fused levels, disc spaces of Cage dislodgement, and visual analogue scale (VAS) scores of low back pain and leg pain, Oswestry disability index (ODI), the segmental lordosis (SL) and disc height (DH) of the disc space of Cage dislodgement, and the lumbar lordosis (LL) before revision ( P>0.05). The operation time, intraoperative blood loss, hospital stay, and complications of the two groups were recorded and compared. The VAS scores of low back pain and leg pain were evaluated at 3 days, 3, 6, and 12 months after operation, and the ODI scores were evaluated at 3, 6, and 12 months after operation. The SL and DH of the disc space of Cage dislodgement and LL were measured at 12 months after operation and compared with those before operation. CT examination was performed at 12 months after operation, and the fusion of the disc space implanted with new Cage was judged by Bridwell grading standard. RESULTS: The intraoperative blood loss in the OLIF group was significantly less than that in the PLIF group ( t=-12.425, P=0.000); there was no significant difference between the two groups in the operation time and hospital stay ( P>0.05). Both groups were followed up 12-30 months, with an average of 18 months. In the OLIF group, 2 patients (11.1%) had thigh numbness and 1 patient (5.6%) had hip flexor weakness after operation; 2 patients (9.1%) in the PLIF group had intraoperative dural sac tear. The other patients' incisions healed by first intention without early postoperative complications. There was no significant difference in the incidence of complications between the two groups ( χ 2=0.519, P=0.642). The VAS scores of low back pain and leg pain, and the ODI score of the two groups at each time point after operation were significantly improved when compared with those before operation ( P<0.05); there was no significant difference between the two groups at each time point after operation ( P>0.05). At 12 months after operation, SL, LL, and DH in the two groups were significantly increased when compared with preoperative ones ( P<0.05); SL and DH in the OLIF group were significantly improved when compared with those in the PLIF group ( P<0.05), and there was no significant difference in LL between the two groups ( P>0.05). CT examination at 12 months after operation showed that all the operated disc spaces achieved bony fusion. According to the Bridwell grading standard, 12 cases were grade Ⅰ and 6 cases were grade Ⅱ in the OLIF group, and 13 cases were grade Ⅰ and 9 cases were grade Ⅱ in the PLIF group; there was no significant difference between the two groups ( Z=-0.486, P=0.627). During follow-up, neither re-displacement or sinking of Cage, nor loosening or fracture of internal fixation occurred. CONCLUSION: OLIF and PLIF can achieve similar effectiveness in the treatment of Cage dislodgement after lumbar surgery. OLIF can further reduce intraoperative blood loss and restore the SL and DH of the disc space of Cage dislodgement better.


Subject(s)
Lumbar Vertebrae , Spinal Fusion , Female , Humans , Lumbar Vertebrae/surgery , Lumbosacral Region/surgery , Male , Retrospective Studies , Spinal Fusion/methods , Spinal Fusion/standards , Treatment Outcome
8.
Exp Cell Res ; 393(2): 112109, 2020 08 15.
Article in English | MEDLINE | ID: mdl-32464126

ABSTRACT

The transplantation of bone marrow mesenchymal stem cells (BMSCs) has been found to be used as an effective therapy of intervertebral disc degeneration (IDD). However, the underlying mechanisms of BMSCs in the progress of IDD are not fully explained. In this study, we found that exosomes derived from BMSCs (BMSCs-Exos) inhibited the apoptotic rate, extracellular matrix (ECM) degradation, and fibrosis deposition in TNF-α-induced nucleus pulposus cells (NPCs). Importantly, the level of miR-532-5p was observed to be decreased in apoptotic NPCs, but abundant in BMSCs-Exos with TNF-α treatment. The results showed that BMSCs-Exos under TNF-α stimuli exerted better effects on NPCs than BMSCs-Exos, which might be mitigated by the inhibition of miR-532-5p in BMSCs-Exos. The gain-of-function results suggested that the direct overexpression of miR-532-5p in NPCs could inhibit TNF-α-induced increase of apoptotic process, activation of apoptotic proteins, imbalance of anabolism/catabolism levels, and accumulation of collagen I. In addition, RASSF5 was demonstrated to be a target of miR-532-5p. Knockdown of RASSF5 could decrease the apoptotic cells and reduce the activated apoptotic protein levels in TNF-α-induced NPCs. Overall, these data indicate that exosomes from BMSCs may suppress TNF-α-induced apoptosis, ECM degradation, and fibrosis deposition in NPCs through the delivery of miR-532-5p via targeting RASSF5. This work provides a promising therapeutic strategy for the progress of IDD.


Subject(s)
Bone Marrow Cells/cytology , Mesenchymal Stem Cells/cytology , MicroRNAs/genetics , Tumor Suppressor Proteins/metabolism , Animals , Apoptosis/drug effects , Cell Death/physiology , Exosomes/genetics , Exosomes/metabolism , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Male , Nucleus Pulposus/metabolism , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/genetics
9.
Biomed Pharmacother ; 123: 109738, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31951975

ABSTRACT

OBJECTIVE: To explore the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in vivo and in vitro and its mechanism. METHODS: 60 rats were underwent surgery to construct rat models of IVDD and divided in the sham group, model group and gradient G-Rg1 groups (10 mg/kg/d, 20 mg/kg/d and 40 mg/kg/d).The change of histology was observed by HE staining, the water content and the expression of ß-catenin in IVD were detected. Rat nucleus pulposus cells(NPCs) were isolated from IVDD rats and divided in D-NPCs group, and gradient G-Rg1 groups(20 µg/ml, 50 µg/ml and 100 µg/ml).The cell proliferation activity, cell apoptosis rate,the expression of proteins related to ECM and Wnt/ß-catenin were detected respectively, Finally the agonist of Wnt/ß-catenin pathway LiCl was used for reversed experiments. RESULTS: In vivo, G-Rg1 treatment could improve the structural disorganization, low water content, NPCs number and aggrecan and collagenⅡ expression in IVD and down-regulate the expression of ß-catenin. In vitro NPCs, G-Rg1 treatment could improve the low cell proliferation, high apoptosis rate and low expression of aggrecan and collagenⅡ in degenerative NPCs in a dose-dependent manner.G-Rg1 treatment could down-regulate the expression of proteins related to ß-catenin signal and LiCl could reverse the increase of cell proliferation and ECM synthesis, decrease of apoptosis of degenerative NPCs induced by G-Rg1. CONCLUSION: G-Rg1 could promote ECM synthesis of degenerative NPCs and inhibiting its apoptosis, improve the IVDD via inhibiting the Wnt/ß-catenin pathway.


Subject(s)
Ginsenosides/pharmacology , Intervertebral Disc Degeneration/metabolism , Nucleus Pulposus/metabolism , Aggrecans/metabolism , Animals , Apoptosis , Cell Proliferation , Collagen/metabolism , Cyclin D1/metabolism , Intervertebral Disc Degeneration/pathology , Male , Models, Animal , Proto-Oncogene Proteins c-myc/metabolism , Rats , Rats, Sprague-Dawley , Wnt Signaling Pathway , beta Catenin/metabolism
10.
J Mol Neurosci ; 68(2): 181-190, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30911940

ABSTRACT

Microglial activation and inflammatory response played an important role in the secondary injury of spinal cord injury (SCI). Several microRNAs were associated with this procedure, but the underlying molecular mechanism was poorly understood. Sprague-Dawley (SD) rats were divided into four groups: SCI group (n = 7), agomiR-325-3p group (n = 7), and their control groups. Expression of miR-325-3p and proteins in epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway was evaluated in microglia from SCI rats and primary microglia/BV2 cells activated by lipopolysaccharide (LPS). Concentrations of interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in supernatants were measured by ELISA. Low expression of miR-325-3p and activation of EGFR/MAPK was observed in microglia of SCI and LPS-induced primary microglia. Overexpression of miR-325-3p in LPS-induced BV2 cells inhibited microglial activation and release of TNF-α and IL-1ß. Luciferase reporter assay confirmed that miR-325-3p negatively regulated EGFR by targeting its 3'-untranslated regions. Additionally, agomiR-325-3p inhibited the activation of microglia and EGFR/MAPK, alleviating the inflammatory response. These results indicated that miR-325-3p attenuated secondary injury after SCI through inhibition of EGFR/MAPK signaling pathway, the microglial activation, and the release of inflammatory cytokines, suggesting that miR-325-3p may be employed as a therapeutic target for SCI.


Subject(s)
ErbB Receptors/metabolism , MAP Kinase Signaling System , MicroRNAs/genetics , Microglia/metabolism , Spinal Cord Injuries/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Cell Line , Cells, Cultured , ErbB Receptors/genetics , Interleukin-1beta/metabolism , Lipopolysaccharides/pharmacology , Male , Mice , MicroRNAs/metabolism , Microglia/drug effects , Rats , Rats, Sprague-Dawley , Spinal Cord Injuries/genetics
11.
IUBMB Life ; 71(5): 611-618, 2019 05.
Article in English | MEDLINE | ID: mdl-30592131

ABSTRACT

Long noncoding RNAs (LncRNAs) may serve as miRNA sponges to regulate the expressions of miRNA target genes. LncRNA LINC00969 has been indicated to be upregulated in intervertebral disk degeneration. However, the regulatory mechanism of LINC00969 in intervertebral disk degeneration progression remains unclear. Differently expressed LINC00969, miR-335-3p, and thioredoxin-interacting protein (TXNIP) were determined in nucleus pulposus (NP) tissues and cells isolated from patients with intervertebral disk degeneration. The interaction between LINC00969, miR-335-3p, and TXNIP was also assessed. In this study, we demonstrated that LINC00969 was highly expressed, whereas miR-335-3p was aberrantly downregulated in NP tissues and cells of intervertebral disk degeneration patients. In addition, our results suggested that LINC00969 enhanced NP cell apoptosis. More importantly, LINC00969 was identified to function as a competitive endogenous RNA (ceRNA) for miR-335-3p to positively regulate TXNIP expression in vitro. Our study provided evidence for the cross-talk between LINC00969, miR-335-3p, and TXNIP, shedding light on the therapy for intervertebral disk degeneration. © 2018 IUBMB Life, 71(5):611-618, 2019.


Subject(s)
Gene Expression Regulation , Inflammasomes , Intervertebral Disc Degeneration/pathology , MicroRNAs/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , RNA, Long Noncoding/genetics , Spinal Cord Injuries/pathology , Case-Control Studies , Humans , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Prognosis , Spinal Cord Injuries/genetics , Spinal Cord Injuries/metabolism
12.
Medicine (Baltimore) ; 97(40): e12680, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30290656

ABSTRACT

Spinal fusion has become a standard treatment for symptomatic intervertebral degenerative disc disease. The present study aimed to compare perioperative parameters, clinical outcomes, and radiographic results of stand-alone oblique lumbar interbody fusion (OLIF) with posterior lumbar interbody fusion (PLIF) for the revision of rostral adjacent segment disease (ASD) following prior posterior lumbar fusion.Thirty-six patients who underwent revision surgeries for rostral ASD were retrospectively reviewed. Among them, 17 patients underwent stand-alone OLIF (OLIF group) and 19 patients underwent PLIF (PLIF group). The length of operation, intraoperative hemorrhage, bed rest duration, and length of hospital stay were compared between the 2 groups. Clinical results were evaluated with the Oswestry Disability Index (ODI) and visual analog scale (VAS). Radiological results were evaluated with disc height (DH), foraminal height (FH), retrolisthesis index (RI), and lumbar lordosis (LL), as well as the fusion rate and cage subsidence. Follow-up results at 1 week, 3 months, and 12 months postoperatively were compared between the 2 groups.The OLIF group had less intraoperative blood loss, shorter operative time, bed rest time, and hospital stay than did the PLIF group (P < .05). The OLIF group had lower VAS scores for back pain than the PLIF group at 1 week and 3 months postoperatively (P < .05), and lower VAS scores for leg pain than the PLIF group at 1 week postoperatively (P < .05). The OLIF group had lower ODI than the PLIF group at 1 week and 3 months postoperatively (P < .05). No significant differences were found in DH and FH between the 2 groups preoperatively (P > .05); the OLIF group showed higher DH and FH than the PLIF group at all time points (P < .05). No significant differences were found in RI and LL between the 2 groups at any time point. All patients achieved fusion at 12 months postoperatively, and cage subsidence was not observed in either group.OLIF is effective and safe for the treatment of rostral ASD following prior posterior lumbar fusion, and is superior to PLIF in terms of perioperative parameters, short-term clinical outcomes, and DH restoration, with similar fusion and reduction rates.


Subject(s)
Lumbar Vertebrae/surgery , Postoperative Complications/surgery , Reoperation/methods , Spinal Fusion/methods , Aged , Body Mass Index , Female , Humans , Intervertebral Disc Degeneration/surgery , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Retrospective Studies , Spinal Fusion/adverse effects
13.
Chin Med J (Engl) ; 130(21): 2563-2568, 2017 Nov 05.
Article in English | MEDLINE | ID: mdl-29067955

ABSTRACT

BACKGROUND: Lateral compartmental osteoarthritis (LCOA), a major complication after medial mobile-bearing unicompartmental knee arthroplasty (UKA), is highly associated with the increased stress of the lateral compartment. This study aimed to analyze the effects on the stress and load distribution of the lateral compartment induced by lower limb alignment and coronal inclination of the tibial component in UKA through a finite element analysis. METHODS: Eight three-dimensional models were constructed based on a validated model for analyzing the biomechanical effects of implantation parameters on the lateral compartment after medial Oxford UKA: postoperative lower limb alignment of 3° valgus, neutral and 3° varus, and the inclination of tibial components placed in 4°, 2° valgus, square, and 2° and 4° varus. The contact stress of femoral and tibial cartilage and load distribution were calculated for all models. RESULTS: In the 3° valgus lower limb alignment model, the contact stress of femoral (3.38 MPa) and tibial (3.50 MPa) cartilage as well as load percentage (45.78%) was highest compared to any other model, and was increased by 36.75%, 47.70%, and 27.63%, respectively when compared to 3° varus. In the condition of a neutral position, the outcome was comparable for the different tibial tray inclination models. The inclination did not greatly affect the lateral compartmental stress and load distribution. CONCLUSIONS: This study suggested that slightly varus (undercorrection) lower limb alignment might be a way to prevent LCOA in medial mobile-bearing UKA. However, the inclination (4° varus to 4° valgus) of the tibial component in the coronal plane would not be a risk factor for LCOA in neutral position.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Adult , Arthroplasty, Replacement, Knee/methods , Biomechanical Phenomena , Finite Element Analysis , Humans , Knee Prosthesis , Male , Osteoarthritis, Knee/surgery , Tibia/surgery
14.
Chin Med J (Engl) ; 128(21): 2873-8, 2015 Nov 05.
Article in English | MEDLINE | ID: mdl-26521784

ABSTRACT

BACKGROUND: Controversies about the rational positioning of the tibial component in unicompartmental knee arthroplasty (UKA) still exist. Previous finite element (FE) studies were rare, and the results varied. This FE study aimed to analyze the influence of the tibial component coronal alignment on knee biomechanics in mobile-bearing UKA and find a ration range of inclination angles. METHODS: A three-dimensional FE model of the intact knee was constructed from image data of one normal subject. A 1000 N compressive load was applied to the intact knee model for validating. Then a set of eleven UKA FE models was developed with the coronal inclination angles of the tibial tray ranging from 10° valgus to 10° varus. Tibial bone stresses and strains, contact pressures and load distribution in all UKA models were calculated and analyzed under the unified loading and boundary conditions. RESULTS: Load distribution, contact pressures, and contact areas in intact knee model were validated. In UKA models, von Mises stress and compressive strain at proximal medial cortical bone increased significantly as the tibial tray was in valgus inclination >4°, which may increase the risk of residual pain. Compressive strains at tibial keel slot were above the high threshold with varus inclination >4°, which may result in greater risk of component migration. Tibial bone resection corner acted as a strain-raiser regardless of the inclination angles. Compressive strains at the resected surface slightly changed with the varying inclinations and were not supposed to induce bone resorption and component loosening. Contact pressures and load percentage in lateral compartment increased with the more varus inclination, which may lead to osteoarthritis progression. CONCLUSIONS: Static knee biomechanics after UKA can be greatly affected by tibial component coronal alignment. A range from 4° valgus to 4° varus inclination of tibial component can be recommended in mobile-bearing UKA.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Finite Element Analysis , Knee Joint/surgery , Tibia/surgery , Adult , Humans , Male , Stress, Mechanical , Treatment Outcome
15.
Arch Orthop Trauma Surg ; 135(5): 709-13, 2015 May.
Article in English | MEDLINE | ID: mdl-25750137

ABSTRACT

OBJECTIVE: Drainage is a common procedure in unicompartmental knee arthroplasty (UKA), but evidence regarding its effectiveness is lacking. The aim of this study was to investigate the benefits of drainage after minimally invasive UKA with effective blood loss management. METHODS: This was a prospective, randomized, controlled trial to determine whether drainage after UKA provides benefits with respect to blood loss, drainage volume, complications, pain score, knee score, range of motion and cost. The 96 patients who underwent surgery between January 2012 and March 2013 were randomly divided into two groups: group A (n = 48) was treated without drainage, and group B (n = 48) with drainage. All UKA procedures were performed with the same minimally invasive surgical technique. Tranexamic acid and bone wax were used for the management of blood loss in all patients. The preoperative baseline parameters of the two groups did not differ significantly. RESULTS: The mean drainage volume in group B was 75.7 ± 51.2 mL when the drainage was present. Total blood loss in group A and group B was 240.3 ± 73.3 mL and 274.1 ± 99.5 mL, respectively. These amounts did not differ significantly but both were significantly lower than the data reported for total knee arthroplasty. There was no difference in mean postoperative hemoglobin and hematocrit between groups. Differences in wound infection, incidence of deep vein thrombosis, postoperative Hospital for Special Surgery knee score, visual analog score, and range of motion were not statistically significant between groups. Hospitalization costs for UKA were lower in the absence of drainage. CONCLUSIONS: The use of drainage in unilateral UKA provides no apparent advantage. With effective blood loss management and a minimally invasive procedure, blood loss and drainage volume in UKA are very low. Drainage does not improve the results. Foregoing non-drainage after UKA reduces both hospital costs and visible blood loss. Therefore, drainage is unnecessary in routine UKA.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Drainage , Knee Joint/surgery , Postoperative Care , Aged , Aged, 80 and over , Female , Hematocrit , Hemoglobins/analysis , Hospitalization/economics , Humans , Male , Middle Aged , Postoperative Hemorrhage/prevention & control , Prospective Studies
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