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Estrogen and mechanical forces are positive regulators for osteoblast proliferation and bone formation. We investigated the synergistic effect of estrogen and flow-induced shear stress on signal transduction and gene expression in human osetoblast-like MG63 cells and primary osteoblasts (HOBs) using activations of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) and expressions of c-fos and cyclooxygenase-2 (I) as readouts. Estrogen (17β-estradiol, 10 nM) and shear stress (12 dyn/cm2) alone induced transient phosphorylations of ERK and p38 MAPK in MG63 cells. Pretreating MG63 cells with 17β-estradiol for 6 hours before shearing augmented these shear-induced MAPK phosphorylations. Western blot and flow cytometric analyses showed that treating MG63 cells with 17β-estradiol for 6 hrs induced their β1-integrin expression. This estrogen-induction of β1-integrin was inhibited by pretreating the cells with a specific antagonist of estrogen receptor ICI 182,780. Both 17β-estradiol and shear stress alone induced c-fos and Cox-2 gene expressions in MG63 cells. Pretreating MG63 cells with 17β-estradiol for 6 hrs augmented the shear-induced c-fos and Cox-2 expressions. The augmented effects of 17β-estradiol on shear-induced MAPK phosphorylations and c-fos and Cox-2 expressions were inhibited by pretreating the cells with ICI 182,780 or transfecting the cells with β1-specific small interfering RNA. Similar results on the augmented effect of estrogen on shear-induced signaling and gene expression were obtained with HOBs. Our findings provide insights into the mechanism by which estrogen augments shear stress responsiveness of signal transduction and gene expression in bone cells via estrogen receptor–mediated increases in β1-integrin expression. © 2010 American Society for Bone and Mineral Research.

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Inflammation has been proposed to be an important causative factor in ligamentum flavum hypertrophy. However, the mechanisms of mechanical load on inflammation of ligamentum flavum remain unclear. In this study, we used an in vitro model of human ligamentum flavum fibroblasts subjected to centrifugal force to elucidate the effects of mechanical load on cultured human ligamentum flavum fibroblasts; we further studied its molecular and biochemical mechanisms. Human ligamentum flavum fibroblasts were obtained from six patients undergoing lumbar spine surgery. Monolayer cultures of human ligamentum flavum fibroblasts were subjected to different magnitudes of centrifugal forces. Cell viability, cell death, biochemical response, and molecular response to centrifugal forces were analyzed. It was found that centrifugal stress significantly suppressed cell viability without inducing cell death. Centrifugal force at 67.1 g/cm(2) for 60 min significantly increases the production of prostaglandin E2 and nitric oxide as well as gene expression of proinflammatory cytokines, including interleukin (IL)-1α, IL-1β and IL-6, showed that centrifugal force-dependent induction of cyclooxygense-2 and inducible NO synthase required JNK and p38 mitogen-activated protein kinase, but not ERK 1/2 activities. This study suggested that centrifugal force does induce inflammatory responses in human ligamentum flavum fibroblasts. The activation of both JNK and p38 mitogen-activated protein kinase mechanotransduction cascades is a crucial intracellular mechanism that mediates cyclooxygense-2/prostaglandin E2 and inducible NO synthase/nitric oxide production.

The dispatchers should spend more time identifying stroke patients by following the dispatch protocol. Recognition of stroke by dispatchers was associated with improved stroke care.

Objectives To disclose the link between the composition of urolithiasis, especially that of uric acid calculi, and obesity, prediabetes, type 2 diabetes mellitus, and hypertension. Materials and MethodsPatients who had urinary calculi and underwent surgical treatment were registered in the study. The composition of urinary calculi was analyzed and correlated with clinical features and biomedical profiles of the patients before surgical intervention. Results A total of 666 patients with urolithiasis who underwent surgical management were registered and analyzed. In those who had uric acid calculi, there was a significant association with prediabetic (OR: 20.11, 95% CI: 7.40–54.63, P < 0.001) and diabetic states (OR: 11.55, 95% CI: 4.41–29.97, P < 0.001). It also seemed that uric acid calculi were related to obesity but there was no statistical significance (OR: 2.45, 95% CI: 0.91–6.62, P = 0.078). There was no association of uric acid calculi with hypertension (OR: 1.08, 95% CI: 0.54–2.17, P = 0.822) and concurrent urinary tract infection (OR: 0.93, 95% CI: 0.44–1.96, P = 0.841). Conclusion There was a remarkable association of uric acid calculi with prediabetic and diabetic states. The uric acid calculi were also seemingly associated with obesity in patients with urolithiasis undergoing surgical management.