Effects of oral administration recombinant Saccharomyces cerevisiae expressing human-salmon calcitonin on hypercalcemia rats~

Recombinant human-salmon calcitonin (hsCT) was synthesized and expressed on the cell surfaces of recombinant Saccharomyces cerevisiae (yAGA2-hsCT) using the pAGA2-hsCT expression vector.Expression of r...     

Effects of the rare earth ions on bone resorbing function of rabbit mature osteoclasts<Emphasis Type="Italic">in vitro</Emphasis>

The osteoclast plays initiating and vanguard roles in the course of bone remodeling. The resorption and formation of bone is the basic clues of bone remodeling, which results from the mutual dependent functions of osteoclasts and osteoblasts. When the osteoclasts are activated, the bone resorption function is increased. The excess bone resorption leads to osteoporosis, characterized by formation of many hollows, lacunae and tunnels on the bone surface or in depth[1,2]. The differentiation, pro…     

反式白藜芦醇对破骨细胞分化的影响

目的:研究反式白藜芦醇对体外破骨细胞分化的影响.方法建立由骨保护素配体(RANKL)和巨噬细胞集落刺激因子(M-CSF)共同细胞因子的小鼠破骨细胞骨髓诱导体系,将不同浓度的反式白藜芦醇作用于破骨细胞.受试细胞分为对照组、反式白藜芦醇低剂量组(10-8mol.L-1)、反式白藜芦醇中剂量组(10-7mol.L-1)和反式白藜芦醇高剂量组(10-6mol.L-1),并设立空白对照组.7 d后取细胞玻片进行抗酒石酸酸性磷酸酶(TRAP)染色,观察破骨细胞并计数;测量抗酒石酸酸性磷酸酶(TRAP)活性以及破骨细胞表面NF-κB活化受体(RANK)mRNA表达量.结果诱导培养的破骨细胞形态特征明显;反式白藜芦醇中、高剂量组在细胞数量、TRAP活性上与对照组相比有明显统计学差异(P<0.05);反式白藜芦醇各剂量组在(RANK)mRNA表达量上与对照组相比有明显统计学差异(P<0.05),且呈量效关系.结论:反式白藜芦醇可以抑制体外培养的破骨细胞分化.     

镧和钆对DU145细胞诱导的前成骨细胞和破骨细胞分化的影响

为探索稀土化合物在防治前列腺癌骨转移方面的潜在药理作用,研究了镧(La)和钆(Gd)对前列腺癌细胞DU145诱导的成、破骨细胞分化的影响.实验结果表明,DU145细胞的条件培养基能够促进小鼠前成骨细胞MC3T3-e1的增殖、ALP活性和钙沉积,而且经La处理后作用进一步加强.然而Gd处理后的DU145细胞条件培养基组对MC3T3-e1的ALP活性和钙沉积影响并不显著.RT-PCR实验表明,La可能通过上调DU145细胞分泌的细胞因子BMP6表达,抑制Noggin的表达进而促进成骨细胞的增殖和分化;而且成骨细胞的增殖、分化与JNK信号转导通路有关.此外,还观察到La能够抑制DU145细胞诱导的破骨细胞生成,并且通过下调前列腺癌细胞RANKL的表达而起到抑制作用.然而Gd对DU145细胞诱导的破骨细胞生成的影响并不显著.     

聚甲基丙烯酸甲酯颗粒诱导假体周围骨溶解的实验研究

通过破骨细胞培养及动物模型,探讨颗粒诱导假体周围骨质溶解的机制。取SD仔鼠骨髓细胞,在聚甲基丙烯酸甲酯(PMMA)颗粒的刺激下,进行体外破骨细胞培养,然后行TRAP染色,观察颗粒对破骨细胞形态的影响;对骨片上形成的骨吸收陷窝行甲苯胺蓝染色观察并计数。选用24只BALB/c小鼠,在小鼠颅骨部位注入PMMA颗粒,建立骨吸收动物模型。按照注入颗粒的不同随机分为2组,即实验组和对照组,每组12只。2周后处死动物并取材,行HE染色、TRAP染色及TNF-α免疫组化检查。结果显示,PMMA颗粒在体外条件下实验组TRAP染色阳性细胞数及骨吸收陷窝数均较对照组多。动物模型结果显示实验组有明显的骨吸收现象,而对照未发现明显的骨吸收;免疫组化检测亦显示实验组TNF-α较对照组明显。说明PMMA颗粒可诱导假体周围骨质溶解,继而引发假体松动。     

RANKL,RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases

1997 saw the identification of a novel set of proteins within the tumor necrosis factor (TNF)/TNF receptor families that are required for the control of bone remodeling. Therefore, these receptors, receptor activator of nuclear factor kappa B (RANK), osteoprotegerin (OPG) and their ligand RANK ligand (RANKL) became the critical molecular triad controlling osteoclastogenesis and pathophysiologic bone remodeling. However, the establishment of the corresponding knock-out and transgenic mice revealed unexpected results, most particularly, the involvement of these factors in the vascular system and immunity. Thus, the OPG/RANK/RANKL molecular triad appears to be associated with vascular calcifications and plays a pivotal function in the development of the immune system through dendritic cells. OPG/RANK/RANKL thus constitute a molecular bridge spanning bone metabolism, vascular biology and immunity. This review summarizes recent knowledge of OPG/RANK/RANKL interactions and activities as well as the current evidence for their participation in osteoimmunology and vascular diseases. In fine, the targeting of the OPG/RANK/RANKL axis as novel therapeutic approaches will be discussed. Received 27 February 2007; accepted 4 April 2007     

Etiologic factors in Paget’s disease of bone

Paget’s disease of bone is a chronic focal skeletal disorder characterized by increased bone resorption by the osteoclasts. Paramyxoviral gene products have been detected in pagetic osteoclasts. Paget’s disease is an autosomal dominant trait with genetic heterogeneity. Several mutations in the ubiquitin-associated (UBA) domain of sequestosome 1 (SQSTM1/p62) have been identified in patients with Paget’s disease. Similarly, mutations in the valosin-containing protein (VCP) gene have been shown to cause inclusion body myopathy associated with Paget’s disease of bone and frontotemporal dementia. In addition, gene polymorphisms and enhanced levels of cytokine/growth factors associated with Paget’s disease have been identified. However, the etiologic factors in Paget’s disease remain elusive. A cause and effect relationship for the paramyxoviral infection and SQSTM1/ p62 gene mutations responsible for pagetic osteoclast development and disease severity are unclear. This article will highlight the etiologic factors involved in the pathogenesis of Paget’s disease. Received 6 October 2005; received after revision 2 November 2005; accepted 24 November 2005