orlistat and Bone-Diseases

To investigate the expression of pyruvate kinase M2 (PKM2) in bone marrow mesenchymal stem cells (BMSCs) in myeloma bone disease (MBD) and its effect on osteogenic and adipogenic differentiation of BMSCs.. BMSCs were isolated from bone marrow of five patients with multiple myeloma (MM) (MM group) and five with iron deficiency anemia (control group) for culture and identification. The expression of PKM2 protein were compared between the two groups. The differences between osteogenic and adipogenic differentiation of BMSCs were assessed by using alkaline phosphatase (ALP) and oil red O staining, and detecting marker genes of osteogenesis and adipogenesis. The effect of MM cell line (RPMI-8226) and BMSCs co-culture on the expression of PKM2 was explored. Functional analysis was performed to investigate the correlations of PKM2 expression of MM-derived BMSCs with osteogenic and adipogenic differentiation by employing PKM2 activator and inhibitor. The role of orlistat was explored in regulating PKM2 expression, osteogenic and adipogenic differentiation of MM-derived BMSCs.. Compared with control, MM-originated BMSCs possessed the ability of increased adipogenic and decreased osteogenic differentiation, and higher level of PKM2 protein. Co-culture of MM cells with BMSCs markedly up-regulated the expression of PKM2 of BMSCs. Up-regulation of PKM2 expression could promote adipogenic differentiation and inhibit osteogenic differentiation of MM-derived BMSCs, while down-regulation of PKM2 showed opposite effect. Orlistat significantly promoted osteogenic differentiation in MM-derived BMSCs via inhibiting the expression of PKM2.. The overexpression of PKM2 can induce the inhibition of osteogenic differentiation of BMSCs in MBD. Orlistat can promote the osteogenic differentiation of BMSCs via inhibiting the expression of PKM2, indicating a potential novel agent of anti-MBD therapy.. PKM2对骨髓瘤骨病骨髓间充质干细胞成骨与成脂分化的影响.. 探讨骨髓瘤骨病（MBD）中骨髓间充质干细胞（BMSC）丙酮酸激酶M2型（PKM2）表达变化及其对BMSC成骨、成脂分化的影响.. 抽取5例多发性骨髓瘤（MM）与5例缺铁性贫血（对照组）患者骨髓，分离BMSC进行培养与鉴定。比较MM与对照组患者BMSC的PKM2蛋白表达，通过检测成骨、成脂分化标志基因表达，碱性磷酸酶与油红O染色等分析成骨、成脂分化差异，探讨MM细胞与BMSC共培养对PKM2表达影响。通过PKM2激动剂与抑制剂的功能分析，探讨MM-BMSC的PKM2表达与成骨、成脂分化的相关性。探讨奥利司他对MM-BMSC的PKM2表达及成骨成脂分化的作用.. 与对照组相比，MM-BMSC的PKM2蛋白表达明显升高。MM-BMSC细胞具有成骨分化受抑而成脂分化增多的特性。MM细胞与BMSC共培养可诱导BMSC的PKM2表达上调。上调PKM2表达可促进MM-BMSC成脂分化，抑制成骨分化，下调PKM2则显示相反的效应。奥利司他可抑制MM-BMSC的PKM2表达，发挥促进成骨分化作用.. 在MBD中，PKM2过表达可诱导BMSC成骨分化受抑，而奥利司他通过抑制PKM2表达起到促进BMSC成骨分化的作用.

Topics: Adipogenesis; Bone Diseases; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Humans; Mesenchymal Stem Cells; Multiple Myeloma; Orlistat; Osteogenesis; Thyroid Hormone-Binding Proteins