骨桥蛋白和基质金属蛋白酶-3在卵巢浆液性肿瘤中的表达及意义

目的：探讨骨桥蛋白（OPN）和基质金属蛋白酶-3（MMP-3）在卵巢浆液性肿瘤中的表达和临床意义。方法：采用Eliviion免疫组织化学方法检测54例卵巢浆液性肿瘤组织石蜡块标本中OPN和MMP-3的表达，其中恶性34例，交界性10例，良性10例；并将OPN、MMP-3在卵巢恶性浆液性肿瘤中的表达与其临床病理的关系进行分析。结果：①OPN、MMP-3在卵巢良性、交界性和恶性浆液性肿瘤中的阳性表达率逐渐增高（P〈0.05，P〈0.01）；②OPN、MMP-3在卵巢恶性浆液性肿瘤中的阳性表达率：组织学2、3级高于1级（P〈0.05）；手术分期：晚期（Ⅲ-Ⅳ期）高于早期（I-Ⅱ期）（P〈0.05）；而在其他临床病理的分组间表达差异均无统计学意义（P〉0.05）。③OPN与MMP-3在卵巢浆液性肿瘤中的表达呈显著正相关（r=0.5729，P〈0.01）。结论：OPN、MMP-3与卵巢恶性浆液性肿瘤的发生、发展有关，二者可能共同促进了、卵巢恶性浆液性肿瘤的浸润、转移。     

骨桥蛋白与肿瘤

骨桥蛋白(osteopontin，OPN)是一种磷酸化糖蛋白，是骨骼和牙齿矿化细胞外基质的主要组成成分。它不仅参与骨的吸收与形成，而且与肿瘤的浸润、转移密切相关，甚至有人认为，它既是肿瘤诊断的标记物，又可作为监测肿瘤预后的指标。关于OPN与肿瘤转移及血管生成的研究不多，作者对此作一综述。     

骨软骨瘤和骨恶性肿瘤KAI-1和OPN的表达及临床病理意义

目的骨软骨瘤和骨恶性肿瘤组织中KAI-1和OPN表达水平的临床病理意义。方法20例骨软骨瘤和55例骨恶性肿瘤经脱钙后常规制作石蜡包理切片,KAI-1和OPN染色方法为SP免疫组化法。结果20例骨软骨瘤KAI-1阳性19例(95.0%)、OPN阳性2例(10.0%),55例骨恶性肿瘤KAI-1阳性28例(50.9%)、OPN阳性30例(52.7%),差异均存在高度显著性(P<0.01);KAI-1和OPN在不同类型骨恶性肿瘤中阳性率差异无显著性(P>0.05);组织学分级I级和未转移骨恶性肿瘤KAI-1表达阳性率明显高于组织学分级II级、III级及转移病例(P<0.05或P<0.01),组织学分级I级和未转移病例OPN表达阳性率明显低于组织学分级III级和转移病例(P<0.05);KAI-1和OPN在骨恶性肿瘤中表达呈高度负相关。结论KAI-1和OPN表达可能是反映骨恶性肿瘤发生、进展、生物学行为及预后的重要标记物。     

胚胎着床及其分子调控研究进展

胚胎着床是哺乳动物特有的生殖生理现象,涉及到胚胎和母体卵巢、子宫之间复杂的相互作用和分子信号联系。各种动物在胚胎着床的方式及分子调控机制上各有不同,目前已发现包括由胚胎和子宫内膜分泌合成的多种生殖激素、生长因子、细胞黏附分子和细胞外基质等物质参与了胚胎着床的分子调控过程。本文综述近年来在人类及相关动物胚胎着床的研究进展,并重点阐述在胚胎着床中存在于胚胎滋养层表面与母体子宫内膜上皮表面作用的相关信号联系及分子调控机制,以期对提高妊娠率、防止胎儿早期流产以及开发简便高效的临床避孕措施的研究提供理论依据和借鉴。     

A comparative study of osteopontin and MMP-2 protein expression in peripheral and central giant cell granuloma of the jaw

Introduction

Oral peripheral and central giant cell granulomas are lesions with little-known etiology and pathogenesis.

Regulation by macromolecules of calcium oxalate crystal aggregation in stone formers

Based on the structure of kidney stones, it is likely that they form as aggregations of preformed crystals, mostly calcium oxalate monohydrate (COM). In this study, we examined the ability of a macromolecular mixture isolated from the urine of normal individuals and stone formers to inhibit aggregation of preformed COM seed crystals in a simple ionic solution using measurements of changes in the particle size distribution (PSD) of preformed COM crystal aggregates. We also examined the effect in this assay of a number of synthetic homopolymers, naturally occurring urine macromolecules, and binary mixtures thereof. The macromolecular mixtures from urine of normals and most stone formers reduced the degree of aggregation of the seed crystals, whereas 22% of stone former urine macromolecules either did not disaggregate or actually promoted further aggregation. Stone formers within one family shared this property, but a non-stone forming sibling did not. Polyanions, either synthetic or naturally occurring, induced disaggregation to an extent similar to that exhibited by normal urine macromolecules, while polycations had no effect on the PSD. However, mixing a polyanion, either poly-aspartate or osteopontin, with the polycation poly-arginine, changed their behavior from disaggregation to aggregation promotion. The disaggregating behavior of normal urinary macromolecules provides a defense against aggregation, but a minority of stone forming individuals lacks this defense, which may contribute to stone formation.     

Mitigation of Ectopic Calcification in Osteopontin-Deficient Mice by Exogenous Osteopontin

Ectopic calcification is a major cause of bioprosthetic heart valve failure. New therapeutic opportunities are offered by the growing understanding that ectopic calcification is an actively regulated process involving several key gene products. One of these products, osteopontin (OPN), is a glycosylated phosphoprotein previously shown to inhibit apatite crystal formation, induce carbonic anhydrase II, and promote mineral resorption. In this study, OPN-deficient mice (OPN−/−) were utilized as an in vivo model to stimulate the ectopic calcification of glutaraldehyde-fixed bovine pericardium (GFBP) tissue and to examine OPN delivery and structure-function relationships with respect to its anti-calcific activity. Significant calcification of GFBP tissue was obtained within 7 days of subcutaneous implantation in OPN−/− mice. Direct rescue of the calcification phenotype was achieved by the administration of exogenous recombinant rat, histidine-fused OPN (rat His-OPN) to the implant site via soluble injection (up to 72% mitigation achieved) or adsorption onto the implant materials (up to 91% mitigation achieved). Effects were specific, since neither fibronectin nor polyhistidine alone could mitigate calcification of GFBP. The maximum anti-calcific effect was achieved only when rat His-OPN was adequately phosphorylated and contained a functional arginine-glycine-aspartate (RGD) cell adhesive domain. Furthermore, CAII levels in host cells surrounding GFBP were greatest when phosphorylated, RGD-containing rat His-OPN was adsorbed. These data suggest that both physical inhibition, mediated by phosphorylation sites in OPN, as well as the induction of CAII and mineral regression, mediated by the RGD domain, contribute to the unique ability of OPN to mitigate ectopic calcification of bioprosthetic valve tissue.     

Alendronate inhibits urinary calcium microlith formation in a three-dimensional culture model

Osteoporosis is associated with the pathogenesis of urinary stone formation. Urinary stones are similar to bone diseases such as osteoporosis and bone metabolism in terms of pathogenesis. Bisphosphonates are potent inhibitors of bone resorption, and are used in the management of bone disease. Furthermore, bisphosphonates have a strong affinity for calcium, and a reported inhibitory effect on calcium oxalate crystallization in vitro. Thus, bisphosphonates might also inhibit urinary stone formation. Madin-Darby canine kidney (MDCK) cells form calcium phosphate microliths at the basolateral side in vitro. We investigated the inhibitory effects of new generation bisphosphonates (alendronate and incadronate) on calcium phosphate microlith formation and on the expression of osteopontin, which is an important urinary stone matrix. MDCK cells formed two types of colonies in three-dimensional soft agar culture; dark colonies containing calcium phosphate microliths and clear colonies free from microliths. We applied purified alendronate and incadronate at concentrations of 10^–11, 10^–9, 10^–7 and 10^–5 M to MDCK cells cultured in three-dimensional soft agar and investigated the efficiency of colony formation and the dark colony ratio (number of dark colonies relative to the total number of colonies). The administration of 10^–9 and 10^–7 M alendronate decreased the dark colony ratio compared with controls, whereas incadronate did not significantly alter this colony ratio compared with controls. The expression of osteopontin in cultured cells was inhibited by the 10^–7 M alendronate administration. The present findings show that alendronate inhibits calcium stone formation, suggesting that it is effective in the prevention of urolithiasis.     

Osteopontin expression and microvascular injury in cyclosporine nephrotoxicity

The aim of this study was to evaluate the role of osteopontin (OPN) in cyclosporine (CsA) nephrotoxicity of the human kidney. Renal biopsy samples obtained before and after 1–2 years of CsA treatment were evaluated in 18 children (2.2–13.0 years, 14 males, 4 females) diagnosed with minimal change nephrotic syndrome. The changes in tubular OPN expression between pre- and post-treatment samples were correlated with interstitial macrophage infiltration, transforming growth factor- (TGF-) expression, interstitial fibrosis, and microvascular density. OPN, TGF-, CD68, and CD34 positivity were quantitatively assessed by immunohistochemical staining. Light microscopy showed that interstitial fibrosis developed in two-thirds of patients after CsA treatment. However, CD68-positive macrophages infiltrated minimally in fibrotic areas and were found in only one-third of patients. OPN expression was significantly increased in the glomerular mesangium (P=0.001) and tubules (P=0.025) after CsA treatment, whereas the number of CD34-positive peritubular capillaries decreased (P=0.022). An inverse relationship was observed between tubular OPN expression and microvascular density (r=–0.644). However, tubular OPN expression was not related to proteinuria, interstitial fibrosis, or interstitial or tubular TGF- expression. This study indicates that increased OPN expression may be related to microvascular injury in human CsA nephrotoxicity. It also shows that OPN expression may be used as an early but non-specific marker of CsA toxicity before the manifestation of interstitial fibrosis.     

Spinal root avulsion-induced upregulation of osteopontin expression in the adult rat spinal cord

Osteopontin (OPN) is a secretory adhesive glycoprotein that is expressed in various tissues and plays a role in inflammation and tissue repair. It has been suggested that OPN plays a role in inflammation and wound healing after spinal cord injury; however, the expression of OPN and its function in the spinal cord under normal conditions and following spinal motoneuron injury have not been well characterized. Here we examined the expression of OPN mRNA before and after spinal root avulsion. OPN mRNA was detected at a low level in the normal spinal cord in a Northern blot analysis, but dramatically increased following avulsion. In situ hybridization and immunohistochemical studies demonstrated that OPN was present only in a subset of spinal motoneurons before avulsion. After avulsion, the number of OPN-expressing motoneurons increased, although the total number of motoneurons was reduced. OPN expression also became apparent in activated microglia/macrophages and astrocytes. These data suggest that the upregulation of OPN after spinal root avulsion is involved in two events, the protection of neurons and the post-traumatic inflammatory response in microglia/macrophages and astrocytes.