Reports of the bone-protective effects of resveratrol, a naturally occurring phytoestrogen and agonist for the longevity gene SIRT1, have highlighted this compound as a candidate for therapy of osteoporosis. Moreover, SIRT1 antagonism enhances adipogenesis. There has been speculation that resveratrol can promote osteogenesis through SIRT1, but the mechanism remains unclear. In this study we investigated the molecular mechanism of how resveratrol can modulate the lineage commitment of human mesenchymal stem cells to osteogenesis other than adipogenesis. We found that resveratrol promoted spontaneous osteogenesis but prevented adipogenesis in human embryonic stem cell-derived mesenchymal progenitors. Resveratrol upregulated the expression of osteo-lineage genes RUNX2 and osteocalcin while suppressing adipo-lineage genes PPARg2 and LEPTIN in adipogenic medium. Furthermore, we found that the osteogenic effect of resveratrol was mediated mainly through SIRT1/FOXO3A with a smaller contribution from the estrogenic pathway. Resveratrol activated SIRT1 activity and enhanced FOXO3A protein expression, a known target of SIRT1, in an independent manner. As a result, resveratrol increased the amount of the SIRT1-FOXO3A complex and enhanced FOXO3A-dependent transcriptional activity. Ectopic overexpression or silencing of SIRT1/FOXO3A expression regulated RUNX2 promoter activity, suggesting an important role for SIRT1-FOXO3A complex in regulating resveratrol-induced RUNX2 gene transcription. Further mutational RUNX2 promoter analysis and chromatin immunoprecipitation assay revealed that resveratrol-induced SIRT1-FOXO3A complex bound to a distal FOXO response element (À1269/À1263), an action that transactivated RUNX2 promoter activity in vivo. Taken together, our results describe a novel mechanism of resveratrol in promoting osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis. ß
Screw loosening can threaten pedicle screw fixation of the spine. Conical screws can improve the bending strength, but studies of their pullout strength as compared with that of cylindrical screws have shown wide variation. In the present study, polyurethane foam with two different densities (0.32 and 0.16gm/cm3) was used to compare the pullout strength and stripping torque among three kinds of pedicle screws with different degrees of core tapering. Three-dimensional finite element models were also developed to compare the structural performance of these screws and to predict their pullout strength. In the mechanical tests, pullout strength was consistently higher in the higher density foam and was closely related to screw insertion torque (r = 0.87 and 0.81 for the high and low density foam, respectively) and stripping torque ( r = 0.92 and 0.78, respectively). Conical core screws with effective foam compaction had significantly higher pullout strength and insertion torque than cylindrical core screws (p < 0.05). The results of finite element analyses were closely related to those of the mechanical tests in both situations with or without foam compaction. This study led to three conclusions: polyurethane foam bone yielded consistent experimental results; screws with a conical core could significantly increase pullout strength and insertion torque over cylindrical; and,finite element models could reliubly reflect the results of mechunicul tests.
HMW-HA may have a structure-modifying effect for OA by down-regulation of aggrecanase-2 in FLS. HMW-HA also has an anti-inflammatory effect by down-regulation of TNF-alpha, IL-8, and iNOS in FLS. These effects may be mediated through the interaction of CD44 and HMW-HA.
Increased plantar fascia thickness is common with chronic plantar fasciitis, and reduction of the thickness after extracorporeal shock wave therapy or steroid injection has been reported. We hypothesized a decrease of plantar fascia thickness was associated with pain reduction after extracorporeal shock wave therapy. Fifty-three eligible patients with 78 symptomatic feet were randomly treated with piezoelectric-type extracorporeal shock wave therapy of two intensity levels (0.12 and 0.56 mJ/mm2). Two thousand shock waves for three consecutive sessions were applied at weekly intervals. A visual analog scale for pain, the Foot Function Index, the Short Form-36 Health Survey, and ultrasonographic measurement of plantar fascia thickness were evaluated at baseline and 3 and 6 months after treatment. We analyzed the association between pain level and plantar fascia thickness with generalized estimating equation analysis and adjusted for demographic and treatment-related variables. Patients with thinner plantar fascia experienced less pain after treatment; high-intensity treatment and regular exercise were associated with lower pain level. The overall success rates were 63% and 60% at the 3- and 6-month followups. High- and low-intensity treatments were associated with similar improvements in pain and function. Receiving high-intensity treatment, although associated with less pain at followup, did not provide a higher success rate.
The operative method reported here has the advantages of minimal tissue trauma, minimal hardware application, sufficient fixation, and easy operative technique, and it can be a worthy alternative for the treatment of severely displaced surgical neck fractures of the humerus.
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