Ang Deng

Association between FokI polymorphism in vitamin D receptor gene and susceptibility to spinal tuberculosis in Chinese Han population.

BACKGROUND AND AIMS Studies have shown that the vitamin D receptor (VDR) gene polymorphisms may be associated with pulmonary tuberculosis (TB) and play important roles in the regulation of calcium in a variety of tissues including bone. To our knowledge, however, whether FokI polymorphism in VDR gene is associated with susceptibility to spinal TB is still unknown. We undertook this study to investigate the association between FokI polymorphism in VDR gene and susceptibility to spinal TB in Chinese Han population. METHODS This study included 110 patients with spinal TB and 102 volunteers as controls. FokI polymorphism in VDR gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the spinal TB group and the control group. The frequencies of VDR-FokI genotypes in the two groups were compared using chi(2) test. RESULTS There was a significant difference between groups in regard to the frequencies of the VDR-FokI genotypes (p <0.05). In the spinal TB group, the frequency of the ff genotype was 46.36%, which was significantly higher than the corresponding value for the control group (28.43%). Furthermore, the odds ratio (OR) was 2.176 (p <0.05), and the 95% confidence interval (CI) ranged from 1.236-3.832. CONCLUSIONS FokI polymorphism in VDR gene may be associated with the susceptibility to spinal TB in Chinese Han population. Furthermore, the ff genotype may be the susceptible genotype of spinal TB.

Monocyte chemoattractant protein-1 in spinal tuberculosis: -362G/C genetic variant and protein levels in Chinese patients.

The objective of the study is to explore the possible association of the monocyte chemoattractant protein (MCP)-1-362G/C genetic polymorphism and plasma levels of MCP-1 in patients with spinal tuberculosis (TB). The MCP-1-362G/C (rs2857656) polymorphism and blood levels of MCP-1 in patients with spinal TB and healthy subjects were evaluated and compared. Three hundred thirty-two patients and 336 healthy subjects were genotyped using polymerase chain reaction and Sanger DNA sequencing technology. MCP-1 plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. When comparisons were made between patients and controls, the frequency of the MCP-1-362*C minor allele (55.4% versus 47.5%, P = 0.004, odds ratio [OR] = 1.376, 95% confidence interval [CI]: 1.109-1.706) and the carriers of the MCP-1-362*C allele (80.7% versus 71.4%, P = 0.005, OR = 1. 657, 95% CI: 1.167-2.403) were over-represented in patients. The mean MCP-1 plasma level in spinal TB patients was significantly higher than in controls (154.44 ± 68.81 pg/mL versus 36.69 ± 21.71 pg/mL, t = -5.85, P < 0.001). The patients with the CC genotype had the highest MCP-1 level (150.63 ± 73.89 pg/mL), followed by those with the GC genotype (108.63 ± 52.09 pg/mL, t = 2.351, P = 0.022) and GG (91.29 ± 54.31 pg/mL, t = 3.091, P = 0.003) homozygotes. We report the association of the -362G/C genetic polymorphism and increased plasma levels of MCP-1 in patients with spinal TB and nominate the -362*C minor allele as a risk factor for spinal TB in the Chinese population.

Opposite Function of ERα and ERβ in Controlling 17β-Estradiol-mediated Osteogenesis in Osteoblasts.

Estrogen receptor plays critical roles in osteogenesis but the underlying mechanism remains unclear. In order to determine the effect of ERα and ERβ on several critical factors in regulating osteogenesis in human osteoblasts. Cell based assy, RT-PCR and immunoblot analyses were used in the research. Both RT-PCR and immunoblot showed that gene expression of OPG, MBP2, TGF-β, RUNX2, IGF-1 was significantly reduced while expression of RANKL was drastically increased after shRNA-based depletion of ERα in MG-63 osteoblasts. Surprisingly, 17β-estradiol (E2) treatment led to remarkably reduced RANKL compared with that in E2 untreated cells. In contrast, ERβ plays an opposite role in regulating gene expression of OPG, MBP2, TGF-β, RUNX2, IGF-1 and RANKL. However, double depletion of ERα and ERβ could not rescue the gene expression of these factors in vitro. Our results provide a novel mechanism of estrogen receptor in controlling osteogenesis in human cells as well as a potential clinic therapeutic target in human osteoporosis.

Use of finite element analysis of a Lenke type 5 adolescent idiopathic scoliosis case to assess possible surgical outcomes

Objective: To use the finite element model of a Lenke 5 adolescent idiopathic scoliosis (AIS) patient to simulate four corrections (including anterior and posterior correction); to investigate the corrective effect of different surgical protocols; and to analyze the biomechanical stress and strain of the scoliotic spines. Methods: Four surgical strategies were designed and simulated with the model of scoliosis. All the main steps of each strategy, including derotation and compression, were simulated. The stress variation of the spine and the corrective effect were compared among the protocols for different surgical approaches and fusion levels. Results: With the four different surgical protocols, the coronary lumbar deformity was corrected to 22°, 23°, 26° and 26°, respectively, and a physiological sagittal configuration was maintained; however, higher stress was observed with solutions A1 (screw model implanted in the convex side of T12-L3) and A2 (screw model implanted in the convex side of T11-L4), while solution B2 (the posterior approach: T10-L5, fusion to SV) lost too many lumbar movement segments. A similar apical rotational correction was recorded (41.68° and 37.79°) for solutions A2 and B1 (the posterior approach: T10-L4, fusion to LEV), which both instrumented the lower end vertebrae. Conclusions: The presented model could be used successfully to simulate correction procedures, including 90° derotation and compression, for the first time. The Lenke 5 AIS in this particular case was more rigid, and solution B1 was considered the ideal choice for treatment of this patient.

Debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion in the surgical treatment of multilevel noncontiguous spinal tuberculosis in elderly patients via a posterior-only

PURPOSE To analyse the efficacy and feasibility of surgical management for elderly patients with multilevel non-contiguous spinal tuberculosis(MNSTB)by using one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion. METHODS From September 2009 to October 2013, 15 elderly patients with MNSTB were treated with one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion. There were 10 males and 5 females with a mean age of 63.2 years (range: 60-68 years) at the time of surgery. The mean follow-up time was 40 months(range 26-68 months). Patients were evaluated before and after surgery in terms of erythrocyte sedimentation rate(ESR), neurological status, pain and kyphotic angle. RESULTS The spinal tuberculosis was completely cured, and the grafted bones were fused in all 15 patients. There were no recurrent tuberculous infections. The ESR reached a normal level within 3 months in all patients. The ASIA neurological classification improved in all cases, and pain relief was reported by all patients. The average preoperative kyphosis was 20.1° (range 8-38°) and decreased to 7.6° (range 1-18°) postoperatively. There was no significant loss of the correction at the latest follow-up. CONCLUSIONS Our results showed that one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion was an effective treatment for elderly patients with MNSTB. It is characterized by minimum surgical trauma, good neurological recovery, and good correction of kyphosis.

Posterior-only surgical correction of dystrophic scoliosis in 31 patients with neurofibromatosis Type 1 using the multiple anchor point method

OBJECTIVE The objective of this study was to evaluate the clinical efficacy of posterior-only surgical correction of dystrophic scoliosis in patients with neurofibromatosis Type 1 (NF1) using a multiple anchor point method (MAPM). METHODS From 2005 to 2014, 31 patients (mean age 13.5 years old, range 10-22 years old) suffering from dystrophic scoliosis associated with NF1 underwent posterior-only surgical correction using a MAPM. The apex of the deformity was thoracic (n = 25), thoracolumbar (n = 4), and lumbar (n = 2). The mean preoperative coronal Cobb angle was 69.1° (range 48.9°-91.4°). The mean Cobb angle on the side-bending radiograph of the convex side was 58.2° (range 40°-79.8°). The mean flexibility and apical vertebral rotation (AVR) were 15.6% (range 8.3%-28.2%) and 2.5° (range 2°-3°), respectively. The mean angle of sagittal kyphosis was 58.3° (range 34.1°-79.6°). RESULTS The mean follow-up period was 53 months (range 12-96 months). The mean postoperative coronal Cobb angle was 27.4° (range 16.3°-46.7°). Postoperatively, the mean AVR and angle of sagittal kyphosis were 1.2° (range 1°-2°) and 22.4° (range 4.2°-36.3°), respectively. All patients showed good correction of all indices postoperatively. The mean postoperative correction rate was 58.7% (range 46.3%-74.1%). At the final follow-up evaluation, the corrective loss rate of the Cobb angle was only 2.3%. Only 1 patient required revision surgery. No severe complications such as spinal cord, neural, or large vascular injury occurred during the operation. CONCLUSIONS Posterior-only surgical correction of dystrophic scoliosis in patients with NF1 using a MAPM could yield satisfactory clinical efficacy of correction and fusion.

Knockdown of Indian hedgehog protein induces an inhibition of cell growth and differentiation in osteoblast MC3T3‑E1 cells

Indian hedgehog protein (Ihh) is evolutionarily conserved and serves important roles in controlling the differentiation of progenitor cells into osteoblasts. Ihh null mutant mice exhibit a failure of osteoblast development in endochondral bone. Although studies have demonstrated that Ihh signaling is a potent local factor that regulates osteoblast differentiation, the specific transcription factors that determine osteoblast differentiation remain unclear. Further studies are required to determine the precise mechanism through which Ihh regulates osteoblast differentiation. In the present study, Ihh was knocked down in osteoblast MC3T3-E1 cells using short hairpin RNA, to investigate the function of Ihh in osteoblast proliferation and differentiation and to examine the potential mechanism through which Ihh induces osteoblast apoptosis and cell cycle arrest. It was observed that the knockdown of Ihh induced a marked inhibition of cell growth and increased the apoptosis rate compared with the negative control osteoblasts. Downregulation of Ihh resulted in a cell cycle arrest at the G1 to S phase boundary in osteoblasts. In addition, the knockdown of Ihh decreased the alkaline phosphatase activity and mineral deposition of osteoblasts. The inhibitory roles of Ihh downregulation in osteoblast growth and differentiation may be associated with the transforming growth factor-β/mothers against decapentaplegic homolog and tumor necrosis factor receptor superfamily member 11B/tumor necrosis factor ligand superfamily member 11 signaling pathways. Manipulating either Ihh expression or its signaling components may be of benefit for the treatment of skeletal diseases.

Matrix metalloproteinase-1 promoter -1607 bp 1G/2G polymorphism associated with increased risk of spinal tuberculosis in Southern Chinese Han population.

Spinal tuberculosis is the most common form of musculoskeletal tuberculosis. The expression of matrix metalloproteinase‐1 (MMP‐1) is increased in cells with Mycobacterium tuberculosis infection. MMP‐1 plays a curial role in extracellular matrix degradation during the progression of tuberculosis. Although the 1G/2G polymorphism in MMP‐1‐1607 influences its transcription, its role in spinal tuberculosis remains unknown.

The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation

The proliferative rate of chondrocytes affects bone elongation. Chondrocyte hypertrophy is required for endochondral bone formation as chondrocytes secrete factors required for osteoblast differentiation and maturation. Previous studies have demonstrated that the Indian hedgehog (Ihh) signaling pathway is a key regulator of skeletal development and homeostasis. The aim of the present study was to investigate the function of Ihh in chondrocyte proliferation and differentiation, as well as the underlying mechanisms. Ihh was knocked down in mouse chondrocyte cells using short hairpin RNA. Chondrocyte apoptosis and cell cycle arrest were assessed using flow cytometry and the results indicated that knockdown of Ihh significantly inhibited cell growth (P<0.05) and increased apoptosis (P<0.001) compared with negative control cells. Downregulation of Ihh also resulted in cell cycle arrest at G1 to S phase in chondrocytes. It was also observed that knockdown of Ihh decreased alkaline phosphatase activity and mineral deposition of chondrocytes. The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation may be associated with the transforming growth factor-β/mothers against decapentaplegic and osteoprotegerin/receptor activator of nuclear factor κB ligand signaling pathway. The results of the present study suggest that chondrocyte-derived Ihh is essential for maintaining bone growth plates and that manipulation of Ihh expression or its signaling components may be a novel therapeutic technique for the treatment of skeletal diseases, including achondroplasia.