Biomechanical analysis of sandwich vertebrae in osteoporotic patients: finite element analysis

ObjectiveThe aim of this study was to investigate the biomechanical stress of sandwich vertebrae (SVs) and common adjacent vertebrae in different degrees of spinal mobility in daily life.Materials and methodsA finite element model of the spinal segment of T10-L2 was developed and validated. Simultaneously, T11 and L1 fractures were simulated, and a 6-ml bone cement was constructed in their center. Under the condition of applying a 500-N axial load to the upper surface of T10 and immobilizing the lower surface of L2, moments were applied to the upper surface of T10, T11, T12, L1, and L2 and divided into five groups: M-T10, M-T11, M-T12, M-L1, and M-L2. The maximum von Mises stress of T10, T12, and L2 in different groups was calculated and analyzed.ResultsThe maximum von Mises stress of T10 in the M-T10 group was 30.68 MPa, 36.13 MPa, 34.27 MPa, 33.43 MPa, 26.86 MPa, and 27.70 MPa greater than the maximum stress value of T10 in the other groups in six directions of load flexion, extension, left and right lateral bending, and left and right rotation, respectively. The T12 stress value in the M-T12 group was 29.62 MPa, 32.63 MPa, 30.03 MPa, 31.25 MPa, 26.38 MPa, and 26.25 MPa greater than the T12 stress value in the other groups in six directions. The maximum stress of L2 in M-T12 in the M-L2 group was 25.48 MPa, 36.38 MPa, 31.99 MPa, 31.07 MPa, 30.36 MPa, and 32.07 MPa, which was greater than the stress value of L2 in the other groups. When the load is on which vertebral body, it is subjected to the greatest stress.ConclusionWe found that SVs did not always experience the highest stress. The most stressed vertebrae vary with the degree of curvature of the spine. Patients should be encouraged to avoid the same spinal curvature posture for a long time in life and work or to wear a spinal brace for protection after surgery, which can avoid long-term overload on a specific spine and disrupt its blood supply, resulting in more severe loss of spinal quality and increasing the possibility of fractures

MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K.

The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3'-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells

The role of PI3K/AKT pathway in miR-27a induced apoptosis.

<p>(A) Western blot analysis of total PI3KCD, p-AKT, NF-κB, Bcl-2 and cleaved caspase 3 protein levels inhuman NP cells with up-regulation and knockdown of miR-27a. (B) Quantification of band intensity in (A). Results are shown as mean ± SEM. Data are representative of three independent experiments (*P<0.05 vs control).</p

The expression levels of miR-27a were analyzed in human degenerative NP compared with control NP by real-time RT-PCR.

<p>The relative expression of miR-27a was normalized to the endogenous control U6. Each sample was analyzed in triplicate (**<i>P</i> <0.01, ***<i>P</i><0.001). (A) miR-27a is up-regulated in damaged NP <i>in </i><i>vitro</i>. (B) miR-27a is up-regulated in damaged NP cells <i>in </i><i>vivo</i>. Data are representative of six independent experiments. Error bars represent SEM; *<i>P</i><0.05.</p

Apoptosis was increased in the injury model.

<p>(A) Assessment of cell viability by MTT. The cell viability was compared in the different NP cell groups (∗P <0.05). Data are representative of three experiments; error bars represent SEM. (B) Contour diagram of FITC-Annexin V/PI FCM of human NP cells. The graphs represent typical results of cell apoptosis; values represent the means of two experiments. (C) Results of cellular apoptosis was expressed as a fold change. Results are shown as mean ± SEM. Data are representative of three independent experiments (*P<0.05, **P<0.01).</p

Overexpression of miR-27a in nucleus pulposus cells, and its function in the regulation of target proteins

<p>(A) Comparison of cell proliferation in various NP cell groups (*P<0.05). Data are representative of three experiments; error bars represent SEM. (B) Increased expression of cleaved caspase 3 and decreased expression of PIK3CD in the group overexpressing miR-27a compared to the control group (magnification ×200), respectively. Black arrows indicate positive-stained cells. (C) Contour diagram of FITC-Annexin V/PI FCM of human NP cells. The graphs represent typical results of cellular apoptosis; values represent the means of three experiments. Error bars represent SEM. (D) Results of cellular apoptosis was expressed as a fold change. Results are shown as mean ± SEM. Data are representative of three independent experiments (*P<0.05, ***P<0.001). (E) Increased numbers of nucleus pulposus cells were observed to undergo apoptosis in the group overexpressing miR-27a compared to the control group (magnification ×200). (F) (G) After 36 h, cellular protein lysates were prepared and PIK3CD expression was assessed by Western blot. GAPDH was used as an internal loading standard. Results are shown as mean ± SEM. Data are representative of three independent experiments (*P<0.05, **P<0.01).</p

MiR-27a can inhibit PIK3CD by targeting the 3’-UTRs of PIK3CD.

<p>(A) Complementarity between miR-27a and the putative PIK3CD 3’-UTR target site. PIK3CD 3’-mut indicates the PIK3CD 3’-UTRs with three mutation sites (underlined) in miR-27a binding sites. (B) The relative luciferase activities of three independent experiments are shown. Error bars represent SEM; (**P<0.01).</p

Obesity and Risk of Hip Fracture in Adults: A Meta-Analysis of Prospective Cohort Studies

<div><p>Background</p><p>Many observational studies assessed the association between obesity and risk of hip fracture in adults, but reported controversial results. Our goal was to evaluate the association between obesity and risk of hip fracture in adults by conducting a meta-analysis of prospective cohort studies.</p> <p>Methods</p><p>Three databases, PubMed, Embase and Web of Science, were searched through May 2012 to identify eligible cohort studies. Either a fixed- or a random-effects model was used to calculate the pooled relative risk (RR) with its 95% confidence interval (95%CI).</p> <p>Results</p><p>Fifteen prospective cohort studies involving a total 3,126,313 participants were finally included into this meta-analysis. Overall, adults with obesity compared with the normal weight group had a significantly decreased risk of hip fracture (RR: 0.66, 95% CI 0.57 to 0.77, P<0.001). Meta-analyses by the adjusted status of RRs also suggested adults with obesity compared with the reference group had a significantly decreased risk of hip fracture (adjusted RR: 0.48, 95% CI 0.39 to 0.58, P<0.001; unadjusted RR: 0.66, 95% CI 0.56 to 0.78, P<0.001). Subgroup analyses by gender suggested individuals with obesity had a significantly decreased risk for developing hip fracture compared with the reference group in both men (RR 0.54, 95% CI 0.48 to 0.60, P<0.001) and women (RR 0.70, 95% CI 0.58 to 0.84, P<0.001). No evidence of publication bias was observed in this meta-analysis.</p> <p>Conclusions</p><p>This meta-analysis of prospective cohort studies suggests that obesity significantly decreases the risk of hip fracture in adults, and obesity is probably a protective factor of hip fracture in adults.</p> </div

Characteristics of 15 prospective cohort studies included into this meta-analysis.

<p>(BMI, body mass index).</p

Forest plot showed an association between adult obesity and decreased risk of hip fracture (Analysis of adjusted RRs).

<p>Forest plot showed an association between adult obesity and decreased risk of hip fracture (Analysis of adjusted RRs).</p