Xiaofei Cheng

Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration

Although mesenchymal stem cells (MSCs) transplantation into the IVD (intervertebral disc) may be beneficial in inhibiting apoptosis of nucleus pulposus cells (NPCs) and alleviating IVD degeneration, the underlying mechanism of this therapeutic process has not been fully explained. The purpose of this study was to explore the protective effect of MSC‐derived exosomes (MSC‐exosomes) on NPC apoptosis and IVD degeneration and investigate the regulatory effect of miRNAs in MSC‐exosomes and associated mechanisms for NPC apoptosis. MSC‐exosomes were isolated from MSC medium, and its anti‐apoptotic effect was assessed in a cell and rat model. The down‐regulated miRNAs in apoptotic NPCs were identified, and their contents in MSC‐exosomes were detected. The target genes of eligible miRNAs and possible downstream pathway were investigated. Purified MSC‐exosomes were taken up by NPCs and suppressed NPC apoptosis. The levels of miR‐21 were down‐regulated in apoptotic NPCs while MSC‐exosomes were enriched in miR‐21. The exosomal miR‐21 could be transferred into NPCs and alleviated TNF‐α induced NPC apoptosis by targeting phosphatase and tensin homolog (PTEN) through phosphatidylinositol 3‐kinase (PI3K)‐Akt pathway. Intradiscal injection of MSC‐exosomes alleviated the NPC apoptosis and IVD degeneration in the rat model. In conclusion, MSC‐derived exosomes prevent NPCs from apoptotic process and alleviate IVD degeneration, at least partly, via miR‐21 contained in exosomes. Exosomal miR‐21 restrains PTEN and thus activates PI3K/Akt pathway in apoptotic NPCs. Our work confers a promising therapeutic strategy for IVD degeneration.

Clinical and radiographic outcomes of bilateral decompression via a unilateral approach with transforaminal lumbar interbody fusion for degenerative lumbar spondylolisthesis with stenosis

BACKGROUND CONTEXT Laminectomy with posterior lumbar interbody fusion (PLIF) has been shown to achieve satisfactory clinical outcomes, but it leads to potential adverse consequences associated with extensive disruption of posterior bony and soft tissue structures. PURPOSE This study aimed to compare the clinical and radiographic outcomes of bilateral decompression via a unilateral approach (BDUA) with transforaminal lumbar interbody fusion (TLIF) and laminectomy with PLIF in the treatment of degenerative lumbar spondylolisthesis (DLS) with stenosis. STUDY DESIGN This is a prospective cohort study. PATIENT SAMPLE This study compared 43 patients undergoing BDUA+TLIF and 40 patients undergoing laminectomy+PLIF. OUTCOME MEASURES Visual analog scale (VAS) for low back pain and leg pain, Oswestry Disability Index (ODI), and Zurich Claudication Questionnaire (ZCQ) score. METHODS The clinical outcomes were assessed, and intraoperative data and complications were collected. Radiographic outcomes included slippage of the vertebra, disc space height, segmental lordosis, and final fusion rate. This study was supported by a grant from The National Natural Science Foundation of China (81572168). RESULTS There were significant improvements in clinical and radiographic outcomes from before surgery to 3 months and 2 years after surgery within each group. Analysis of leg pain VAS and ZCQ scores showed no significant differences in improvement between groups at either follow-up. The mean improvements in low back pain VAS and ODI scores were significantly greater in the BDUA+TLIF group than in the laminectomy+PLIF group. No significant difference was found in the final fusion rate at 2-year follow-up. The BDUA+TLIF group had significantly less blood loss, shorter length of postoperative hospital stay, and lower complication rate compared with the laminectomy+PLIF group. CONCLUSIONS When compared with the conventional laminectomy+PLIF procedure, the BDUA+TLIF procedure achieves similar and satisfactory effects of decompression and fusion for DLS with stenosis. The BDUA+TLIF procedure appears to be associated with less postoperative low back discomfort and quicker recovery.

High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

Effect of Single-Level Transforaminal Lumbar Interbody Fusion on Segmental and Overall Lumbar Lordosis in Patients with Lumbar Degenerative Disease

OBJECTIVE To investigate the ability of transforaminal lumbar interbody fusion (TLIF) to improve lumbar lordosis (LL). METHODS In this retrospective study, 92 patients undergoing single-level TLIF to treat lumbar degenerative disease were divided into a low back pain, radiculopathy, and neurogenic claudication group according to their symptoms. Preoperative and postoperative measures, including segmental LL, whole LL, pelvic incidence (PI), pelvic tilt, thoracic kyphosis, sagittal vertical axis, visual analog scale for back and leg pain, and Oswestry Disability Index, were used to evaluate radiographic and clinical outcomes. RESULTS All clinical parameters were significantly improved after TLIF. There was no significant difference in any radiographic parameters in the low back pain group. In the radiculopathy and neurogenic claudication groups, all radiographic parameters were significantly changed after TLIF except for segmental LL and PI in both groups and pelvic tilt in the radiculopathy group. No statistically significant differences were found in improvement of segmental LL, PI, thoracic kyphosis, and visual analog scale (leg) between the radiculopathy and neurogenic claudication groups, whereas the differences in improvement of whole LL, pelvic tilt, PI-LL, sagittal vertical axis, visual analog scale (back), and Oswestry Disability Index were significant between the 2 groups. CONCLUSIONS For patients with neurogenic leg symptoms owing to single-level lumbar degenerative disease, whole LL was improved after TLIF as a result of spontaneous restoration of lordosis at the unfused lumbar levels.

The compression of L5 nerve root, single or double sites?— radiographic graded signs, intra-operative detect technique and clinical outcomes

Background The L5 nerve root could be compressed at both L4-5 and L5-S1 regions. If L5 nerve root has confirmed compression at L4-5 level and questionable compression at L5-S1 foramina, performing both surgeries at L4-5 and L5-S1 levels may induce unnecessary extra surgery on L5-S1; however, ignoring foraminal stenosis of L5/S1 may require re-exploration. Methods Two hundred seventeen patients with L5 nerve root compressed at L4-5 lateral access were performed with L4-5 decompression and interbody fusion. Lee et al. grade classification was used to assess the foraminal stenosis of L5-S1 preoperatively. Nerve root probe was designed and used to detect if there were foraminal stenosis at L5-S1 level that compressing the exiting L5 nerve root. Visual analog scale (VAS) of low back pain, leg pain and Oswestry Disability Index (ODI) were used to assess clinical outcomes. Results For all of 217 patients who underwent L4-5 surgery, L5-S1 foramina were preoperatively assessed as: grade 0: 125 cases, grade 1: 58 cases, grade 2: 23 cases, and grade 3: 11 cases. After intra-operative L5 nerve root detection, 11/11 patients with grade 3 radiographic foraminal stenosis, 6/23 (26.1%) with grade 2 and 2/58 (3.4%) who had grade 1 underwent L4-5 and L5-S1 transforaminal lumbar interbody fusion (TLIF), the others received only L4-5 TLIF. Compared to pre-operative baseline data, both L4-5 TLIF and L4-5 and L5-S1 TLIF groups had significant decreased VAS of low back pain and leg pain, and ODI at 3 and 24 months after operation. Conclusions We suggested that our novel nerve root probe combined with pre-operative radiographic grade may be helpful to surgeons to identify the single or double compression of L5 nerve root and make a more precise surgical strategy to improve surgical outcome than the method depended on pre-operative radiographic grade alone.

Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein

Objectives Circular RNAs (circRNAs) have been proven to function as competing endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression of miRNA target mRNAs. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of intervertebral disc degeneration (IVDD). Methods The role and mechanism of a circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and degenerative NP tissues from patients and rat models. The interaction between circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of-apoptosis protein (XIAP), was examined. Results The decreased expression of XIAP in the inflammatory cytokines-treated NP cells and the degenerative NP tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix. miR-200c regulated NP cell viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of miR-200c and functioned in NP cells through targeting miR-200c and XIAP. Intradiscal injection of circVMA21 alleviated IVDD in the rat model. Conclusions CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and imbalance between anabolism and catabolism of extracellular matrix through miR-200c-XIAP pathway. It provides a potentially effective therapeutic strategy for IVDD.

Spontaneous Improvement of Compensatory Knee Flexion After Surgical Correction of Mismatch Between Pelvic Incidence and Lumbar Lordosis.

Study Design. A retrospective study. Objective. The aim of this study was to investigate the correlation between pelvic incidence (PI) and lumbar lordosis (LL) mismatch and knee flexion during standing in patients with lumbar degenerative diseases and to examine the effects of surgical correction of the PI-LL mismatch on knee flexion. Summary of Background Data. Only several studies focused on knee flexion as a compensatory mechanism of the PI-LL mismatch. Little information is currently available on the effects of lumbar correction on knee flexion in patients with the PI-LL mismatch. Methods. A group of patients with lumbar degenerative diseases were divided into PI-LL match group (PI-LL ⩽ 10°) and PI-LL mismatch group (PI-LL > 10°). A series of radiographic parameters and knee flexion angle (KFA) were compared between the two groups. The PI-LL mismatch group was further subdivided into operative and nonoperative group. The changes in KFA with PI-LL were examined. Results. The PI-LL mismatch group exhibited significantly greater sagittal vertical axis (SVA), pelvic tilt (PT) and KFA, and smaller LL, thoracic kyphosis (TK), and sacral slope than the PI-LL match group. PI-LL, LL, PI, SVA, and PT were significantly correlated with KFA in the PI-LL mismatch group. From baseline to 6-month follow-up, all variables were significantly different in the operative group with the exception of PI, although there was no significant difference in any variable in the nonoperative group. The magnitude of surgical correction in the PI-LL mismatch was significantly correlated with the degree of spontaneous changes in KFA, PT, and TK. Conclusion. The PI-LL mismatch would contribute to compensatory knee flexion during standing in patients with lumbar degenerative disease. Surgical correction of the PI-LL mismatch could lead to a spontaneous improvement of compensatory knee flexion. The degree of improvement in knee flexion depends in part on the amount of correction in the PI-LL mismatch. Level of Evidence: 3

Analysis of compensatory mechanisms in the pelvis and lower extremities in patients with pelvic incidence and lumbar lordosis mismatch

The objective was to analyze the compensatory effect of the pelvis and lower extremities on sagittal spinal malalignment in patients with pelvic incidence (PI) and lumbar lordosis (LL) mismatch. A series of parameters including PI, LL, PI-LL, thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), knee flexion angle (KFA), tibial obliquity angle (TOA), femoral obliquity angle (FOA), femur pelvis angle (FPA) and pelvic shift (PS) were measured. Patients with PI-LL mismatch were divided into pelvic retroversion group and pelvic retroposition group based on their PT and PS, and then the parameters were compared within the two groups and with the control group. All variables were significantly different when comparing the pelvic retroversion and retroposition group with the control group except for PI, FOA and PS in the pelvic retroversion group. The pelvic retroposition group had significantly greater value of PI-LL, PI, PT, KFA, FOA and PS and contribution ratio of FOA and PS, and smaller value of LL, TK and FPA and contribution ratio of PT, TOA and FPA compared with the pelvic retroversion group. Patients with lesser PI-LL mismatch rely more on hip extension to increase pelvic retroversion while those with greater PI-LL mismatch tend to add extra femoral obliquity. When compensating for larger PI-LL mismatch, the importance of hip extension is decreased and the effect of the knee and ankle joint becomes more important by providing greater femoral incline and relatively lesser ankle dorsiflexion respectively.