Liver X receptors orchestrate osteoblast/osteoclast crosstalk and counteract pathologic bone loss

Osteoporosis is characterized by enhanced differentiation of bone‐resorbing osteoclasts, resulting in a rapid loss of functional trabecular bone. Bone‐forming osteoblasts and osteoblast‐derived osteocytes perform a key role in the regulation of osteoclast development by providing both the pro‐osteoclastogenic cytokine receptor activator of NF‐κB ligand (RANKL) and its natural decoy receptor osteoprotegerin (OPG). By regulating the RANKL/OPG ratio, osteoblasts hence determine the rate of both osteoclast differentiation and bone turnover. Here, we describe a novel role for liver X receptors (LXRs) during the crosstalk of bone‐forming osteoblasts and bone‐resorbing osteoclasts. By using a system of osteoblast/osteoclast cocultures, we identify LXRs as regulator of RANKL expression and the RANKL/OPG ratio in osteoblasts. Activation of LXRs drastically reduced the RANKL/OPG ratio and interfered with osteoblast‐mediated osteoclast differentiation in vitro. During an ovariectomy (OVX)‐induced model of postmenopausal osteoporosis, the application of an LXR agonist shifted the RANKL/OPG ratio in vivo, ameliorated the enhanced osteoclast differentiation, and provided complete protection from OVX‐induced bone loss. These results reveal an unexpected involvement of LXRs in the regulation of bone turnover and highlight a potential role for LXRs as novel targets in the treatment of osteoporosis and related diseases. © 2012 American Society for Bone and Mineral Research.     

Quantitative analysis of regional left ventricular function after myocardial infarction in the pig assessed with cine magnetic resonance imaging

To assess the accuracy of quantitative analysis of global and regional wall motion and wall thickening of the left ventricle with cine magnetic resonance (MR), images obtained in eight pigs before and after myocardial infarction were compared with those obtained using gadolinium diethylenetriaminepen-taacetic acid (Gd-DTPA)-enhanced multislice spin-echo MR imaging and determination of pathology. The region with abnormal wall motion and wall thickening, as determined with cine MR imaging, identified the same region of infarction as indicated by Gd-DTPA-enhanced spin-echo MR imaging and pathology. Within the infarcted region wall motion and wall thickening analyzed with the centerline method were significantly reduced. We conclude that the use of quantitative analysis of cine MR images accurately determines localization and extent of regional left ventricular dysfunction in the infarcted heart in vivo. This analysis using dedicated software including the centerline method allows sequential assessment of regional left ventricular function in normal and infarcted hearts.     

骨骼肌缺血再灌注损伤的机制

目的:对近年来骨骼肌缺血再灌注损伤的发病机制进行综述。资料来源:应用计算机检索MEDLINE、CBM、CNKI数据库及手工检索1998-01/2006-11期间的相关文献。中文检索词包括"骨骼肌,缺血再灌注损伤,发病机制";英文检索词有"Skeletal muscle","ischemia and reperfusion injury","oxygen freeradical","calcium overload"和"neutrophil"。资料选择:共收集到相关文献300篇,阅读全部文章的文题和大部分文章的摘要。选择文献所述内容与骨骼肌缺血再灌注损伤机制相关的文献。排除重复性研究。资料提炼:共得到符合纳入条件的文献55篇,排除145篇。选择其中30篇进行分析,英文24篇,中文6篇。资料综合:骨骼肌缺血再灌注损伤的机制由于有许多因素的介入而变的十分复杂,目前主要以氧自由基学说,钙超载学说和中性粒细胞学说为主,同时也注意到了一氧化氮和细胞凋亡以及微循环的无复流现象在其中的作用。结论:氧自由基学说,钙超载学说,中性粒细胞学说,一氧化氮,细胞凋亡以及微循环的无复流现象在骨骼肌缺血再灌注损伤中起着重要作用。     

三叶鼠尾草中小红参醌丙的结构

从三叶鼠尾草(Salvia trijuga Diels)的干燥根中分得9种结晶性成分,经鉴定为铁锈醇(ferruginol)、柳杉酚(sugiol)及系列高级脂肪酸三十四酸、三十酸、二十八酸、十六酸,另两种酸分别为对羟苯甲酸及氨基酸(dl-homoserine),晶Ⅰ为一新化合物,定名为小红参醌丙(trijuganone C),经光谱分析及化学反应推定其结构为15,16-二氢丹参酸甲酯。