Zhanchun Li

Hypertrophy of Ligamentum Flavum in Lumbar Spine Stenosis Is Associated with Increased miR-155 Level

Hypertrophy of ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS) and is caused mainly by fibrosis. Recent data indicate that miR-155 plays a crucial role in the pathogenesis of different fibrotic diseases. This study aimed to test the hypothesis that miR-155 exerts effects on LF thickness by regulating collagen expression. We found that LF thickness and the expression of collagen I and, collagen III were higher in LF from LSS patients than in LF from lumbar disc herniation (LDH) patients (P < 0.01). The expression of miR-155 was significantly higher in LF from LSS group than in LF from LDH group (P < 0.01). miR-155 level was positively correlated with LF thickness (r = 0.958, P < 0.01), type I collagen level (r = 0.825, P < 0.01), and type III collagen level (r = 0.827, P < 0.01). miR-155 mimic increased mRNA and protein expression of collagen I and collagen III in fibroblasts isolated from LF, while miR-155 sponge decreased mRNA and protein expression of collagen I and III in fibroblasts. In conclusions, miR-155 is a fibrosis-associated miRNA and may play important role in the pathogenesis of LF hypertrophy.

Functional Annotation of Rheumatoid Arthritis and Osteoarthritis Associated Genes by Integrative Genome-Wide Gene Expression Profiling Analysis

Background Rheumatoid arthritis (RA) and osteoarthritis (OA) are two major types of joint diseases that share multiple common symptoms. However, their pathological mechanism remains largely unknown. The aim of our study is to identify RA and OA related-genes and gain an insight into the underlying genetic basis of these diseases. Methods We collected 11 whole genome-wide expression profiling datasets from RA and OA cohorts and performed a meta-analysis to comprehensively investigate their expression signatures. This method can avoid some pitfalls of single dataset analyses. Results and Conclusion We found that several biological pathways (i.e., the immunity, inflammation and apoptosis related pathways) are commonly involved in the development of both RA and OA. Whereas several other pathways (i.e., vasopressin-related pathway, regulation of autophagy, endocytosis, calcium transport and endoplasmic reticulum stress related pathways) present significant difference between RA and OA. This study provides novel insights into the molecular mechanisms underlying this disease, thereby aiding the diagnosis and treatment of the disease.

miR-92a promotes tumor growth of osteosarcoma by targeting PTEN/AKT signaling pathway

MicroRNAs (miRNAs) play critical roles in human cancers including osteosarcoma (OS). miR-92a has been found to be a cancer-related miRNA in many cancer types and it is upregulated in OS cell lines. However, the expression and biological function of miR-92a in OS have not been investigated. In this study, we showed that miR-92a expression was increased in OS tissues, and its high expression was correlated with clinical stage, T classification and histological differentiation. Furthermore, patients with high expression of miR-92a had a significantly poorer survival rate. Functionally, miR-92a overexpression promoted the proliferation and cell cycle progression, and inhibited apoptosis in MG-63 cells. While inhibition of miR-92a showed contrary effects with reduced proliferation, cell cycle arrest at G1 phase and increased apoptosis in U2OS cells. Moreover, we confirmed that miR-92a inhibition reversed the tumor growth of OS cells in nude mice. Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor, was confirmed to be the direct downstream target of miR-92a in OS. Notably, miR-92a consequently regulated the expression of the downstream targets of PTEN/AKT signaling pathway including p-Akt(Ser473), mTOR, p-p27(Thr157) and p-MDM2(Ser166). Furthermore, PTEN knockdown abrogated the functional effects of miR-92a silencing on the proliferation, apoptosis and cell cycle progression in OS cells. Thus, miR-92a that exerts an oncogenic role by targeting PTEN/AKT pathway in OS potentially acts as a biomarker and drug-target.

Fibroblast growth factor-21 concentration in serum and synovial fluid is associated with radiographic bone loss of knee osteoarthritis

Abstract We aimed to evaluate whether FGF-21 concentration in serum and synovial fluid (SF) is associated with radiographic bone loss of knee osteoarthritis (OA). A total of 186 OA patients and 108 controls were recruited. The radiographic bone loss of knee OA was assessed by the Ahlbäck grading scale. FGF-21 concentration in serum and SF was measured by enzyme-linked immunosorbent assay (ELISA). We demonstrated that OA patients had significantly higher serum FGF-21 concentration compared with controls (204.30 [range 158.25–279.16] ng/L vs. 130.72 [range 94.93–218.03] ng/L, p < 0.01). FGF-21 concentration in serum was well correlated with that in paired SF samples (r = 0.668, p < 0.001). In OA patients, those with a higher Ahlbäck grade had significantly higher serum and SF FGF-21 concentration (p < 0.001 for both). FGF-21 concentration in serum and SF was significantly and independently associated with the Ahlbäck grade (r = 0.403, p < 0.001 and r = 0.410, p < 0.001; respectively). These findings indicated that FGF-21 might be a potential biomarker for predicting bone loss of OA. Therapeutic interventions by blocking FGF-21 signaling pathways to delay the degenerative process of OA warrants further investigations.

Correlation between neuropeptide distribution, cancellous bone microstructure and joint pain in postmenopausal women with osteoarthritis and osteoporosis.

OBJECTIVES To explore the relationship between the distribution of neuropeptides, cancellous bone microstructure and joint pain in postmenopausal women with osteoarthritis (OA) and osteoporosis (OP). METHODS Cancellous bone of the femoral head was obtained at the time of hip arthroplasty from 20 postmenopausal women, 10 with OA and 10 with OP. Pain intensity was evaluated using the visual analog scale (VAS) before the operation. The microstructural parameters were measured with micro-CT and the neuropeptides of the cancellous bone were stained by an immunohistochemical method. RESULTS We observed that BV/TV, Tb.Th and Th.N values in the OP were significantly decreased compared to those in the OA. Immunohistochemical analysis revealed that the mean optical density (MOD) values for SP, CGRP, and VIP in the OA group were significantly higher than those in the OP, and the MOD value for NPY in the OA was significantly lower than that in the OP. We also observed that the MOD values for SP were positively correlated with AD, BV/TV, Tb.Th, Tb.N and Conn.D and negatively with MD, Tb.Sp and SMI in all patients. The MOD values for CGRP were positively correlated with AD, BV/TV and Tb.Th. MOD values for VIP were positively correlated with BV/TV and Tb.Th and negatively with SMI. The VAS score was correlated positively with the MOD values for SP, CGRP, VIP and negatively with NPY in all patients. CONCLUSIONS Neuropeptides play an important role in the pathogenesis of OA and OP, which may cause pain and influence the bone microstructure.

Surgical treatment for cervical spondylotic myelopathy in elderly patients: A retrospective study

OBJECTIVE To analyze perioperetive clinical features and outcomes of surgical treatment for cervical spondylotic myelopathy (CSM) in elderly patients. METHODS From 2006 to 2013, we retrospectively reviewed 136 patients with CSM who underwent surgery. The patients were divided into two groups: 70 years or older (elderly group, 58 patients) and younger than 70 years (younger group, 78 patients). The course of disease, surgical outcome, morbidities, and postoperative complications were analyzed. RESULTS In the elderly group, follow-up lasted 9-76 months (mean 39.6 months), the course of disease was 23.7 months (range 4-72 months). Anterior cervical decompression and fusions and posterior laminectomy and fixation were performed in 24 and 34 patients, respectively. The operative time averaged 103 min (range 48-210 min). In the younger group, follow-up lasted 10-71 months (mean 37.8 months), the course of disease was 12.6 months (range 2-58 months). Anterior cervical decompression and fusions and posterior laminectomy and fixation were performed in 75 and three patients, respectively. The prevalence of chronic diseases and postoperative complications were higher in the elderly group than the younger group. The recovery rates of JOA score were 40.82 ± 11.20% in the elderly group and 64.10 ± 22.61% in the younger group. The therapeutic effects of surgery were significantly better for the young patients than for the elderly. CONCLUSION Elderly patients with CSM present long period and serious symptoms, and the degeneration of multiple organs. Surgical decompression for CSM appears to be a beneficial and safe procedure for older patients if properly handled, although the recovery rate is poorer than that of younger patients.

Serum fetuin-A levels are inversely associated with clinical severity in patients with primary knee osteoarthritis

The present study aimed to detect serum fetuin-A levels in knee osteoarthritis (OA) patients and to investigate their correlation with clinical severity. We enrolled 215 knee OA patients and 76 healthy controls. We measured serum fetuin-A levels by enzyme-linked immunosorbent assay and assessed the correlation between serum fetuin-A levels and Kellgren-Lawrence grades as well as Western Ontario and McMaster Universities Arthritis Index scores in OA patients. Our results demonstrated that serum fetuin-A levels were independently and negatively correlated with greater clinical severity in OA patients.

FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma

F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS.

Interleukin-34 Synovial Fluid Was Associated with Knee Osteoarthritis Severity: A Cross-Sectional Study in Knee Osteoarthritis Patients in Different Radiographic Stages

Background Inflammation might play a crucial role in the pathogenesis of osteoarthritis (OA). Interleukin-34 (IL-34) is a well-known proinflammatory cytokine. Objective The objective of this study was to detect IL-34 levels in serum and synovial fluid (SF) of patients with OA and to investigate their correlation with radiographic and symptomatic severity. Methods One hundred and eighty-two OA patients and 69 controls were recruited. IL-34 levels were measured by enzyme-linked immunosorbent assay (ELISA). Radiographic and symptomatic severity of OA was reflected by Kellgren-Lawrence (KL) grades and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores, respectively. Results SF IL-34 levels were independently associated with the KL grade (B = 0.273, 95% CI: 0.150–0.395; P < 0.001). SF IL-34 levels were significantly correlated with WOMAC scores (r = 0.265, 95% CI: 0.123–0.399; P < 0.001). The correlation between SF IL-34 levels and WOMAC scores was still significant after adjusting for confounding factors (B = 0.020, 95% CI: 0.001–0.038; P = 0.035) in OA patients. Conclusions We found that IL-34 levels in SF were significantly associated with the radiographic and symptomatic severity of knee OA.

Cyclic stretch enhances apoptosis in human lumbar ligamentum flavum cells via the induction of reactive oxygen species generation.

Objective: The lumbar ligamentum flavum (LF) is an important part of the spine to maintain the stability of the spine. In this study we aimed to examine whether mechanical force by cyclic stretch could induce apoptosis in human LF cells and investigate the underlying mechanism. Methods: LF cells were isolated from six young patients undergoing spinal surgery and then cultured in vitro. LF cells were subjected to cyclic stretch and the poptosis was detected by flow cytometry. The level of intracellular reactive oxygen species (ROS) and caspase-9 activity were measured. Results: Cyclic stretch at a frequency of 0.5 Hz with 20% elongation induced the apoptosis of human LF cells in vitro, and this was correlated with increased ROS generation and activation of caspase-9. Conclusion: Our study suggests that cyclic stretch-induced apoptosis in human LF cells may be mediated by ROS generation and the activation of caspase-9.