慢性充血性心力衰竭患者血清基质金属蛋白酶与骨桥蛋白变化的相关性研究

目的探讨慢性充血性心力衰竭（CHF）患者血清基质金属蛋白酶（MMPs）及其组织抑制因子（TIMPs）和骨桥蛋白（OPN）的变化及相关性。方法CHF患儿24例，正常对照组15例。采用ELISA法测定血清MMP-9和TIMP-1的含量,ELISA法测定血清OPN的含量，分析MMP-9／TIMP-1值与OPN和左室舒末内径（LVEDD）及射血分数（EF）的关系。结果CHF患者血清MMP-9、MMP-9／TIMP-1值和OPN含量明显增加（P均〈0．01），TIMP-1含量明显减少（P〈0．01），MMP-9／TIMP-1值与OPN含量和LVEDD呈正相关（P〈0．05），与EF呈负相关（P〈0．05）。结论CHF患者MMP-9／TIMP-1值与OPN含量呈明显的正相关；MMP-9／TIMP-1值与OPN含量的变化，可反映心衰的严重程度并加速了心功能的恶化。     

骨桥蛋白在雄性哺乳动物生殖系统中的作用

骨桥蛋白(OPN)为一种多功能的细胞外基质蛋白,在多种组织及体液中广泛表达,参与各项生理及病理过程。同时,OPN也表达于女性及男性的生殖系统,参与了胚胎的着床、生长发育及分化等生殖过程。近年来研究表明,OPN普遍存在于雄性哺乳动物的生殖系统中,并与雄性动物的生育力有着密切的关系,可能影响精子的质量及其受精过程等。对OPN相关功能的研究将有助于解释男性不育的机制,提高辅助生殖技术的成功率。     

拉米夫定对肝癌合并慢性乙型肝炎患者血清OPN水平及肝功能的影响

目的探讨肝癌合并乙型肝炎患者经拉米夫定抗病毒治疗后对外周血骨桥蛋白(OPN)水平与肝功能的影响及其临床意义。方法将42例肝癌晚期合并慢性乙肝患者分为两组:对照组16例,采用保肝、退黄、降酶、增强免疫力等支持治疗。实验组26例,在对照组治疗基础上加用拉米夫定口服100 mg,1次/d,观察治疗前及服药2、4周后患者血清OPN水平及肝功能变化情况。结果实验组血清OPN水平有所下降,但仍处于较高水平,两组间差异无统计学意义(P>0.05)。ALT复常率、HBV-DNA转阴率疗效明显优于对照组,两组间差异有统计学意义(P<0.05)。结论拉米夫定对降低肝癌合并慢性乙肝患者血清OPN水平无意义,但可显著降低ALT、HBV-DNA水平。     

骨桥蛋白在 SLE 肾损害 Th17细胞异常中的作用

目的：探讨骨桥蛋白( OPN)在系统性红斑狼疮(SLE)肾损害患者 Th17细胞异常中的作用。方法取40例健康者和50例 SLE 患者(其中,伴肾损害 SLE 患者25例、无肾损害的 SLE 患者25例的血清和肝素钠抗凝血,用ELISA 法检测血清中 OPN 和白介素-17(IL-17)的表达水平,用流式细胞术检测外周血中 CD3+ CD8- IL-17A + T 细胞的阳性率,并分析各组间差异,以及各因素间的相互关系。结果① SLE 肾损害患者组的 OPN、IL-17水平和 CD3+ CD8-IL-17A + T 细胞阳性率显著高于无肾损害的 SLE 患者组、健康对照组,差异均有统计学意义(P <0．01);无肾损害的 SLE患者组和健康对照组间 OPN、IL-17、CD3+ CD8- IL-17A + T细胞阳性率的差异均无统计学意义(P >0．05)。②血清中OPN 分泌与 IL-17水平、CD3+ CD8- IL-17A + T 细胞阳性率之间均成明显正相关性( P <0．01)。结论外周血中的OPN 对 SLE 肾损害患者的 Th17细胞异常起着重要的调控作用。     

Correlation between calcification and bone sialoprotein and osteopontin in papillary thyroid carcinoma

The correlation between calcification and papillary thyroid carcinoma has received increasing attention. We investigated the ability of bone sialoprotein (BSP) and osteopontin (OPN) protein levels to diagnose papillary thyroid carcinoma (PTC), and explored the correlation between BSP and OPN protein levels and calcification in PTC. Archival PTC specimens from patients with PTC with calcification and lateral cervical lymph node metastasis (LNM) were included in this retrospective immunohistochemical study. The protein levels of BSP and OPN were analysed immunohistochemically using routinely prepared tissue sections. PTC specimens from 66 patients with PTC were reviewed retrospectively (25 patients with histological calcification seen in paraffin sections, 41 patients without calcification; 35 patients with lateral cervical LNM, 31 patients without LNM). The percentage of samples that had cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules, and adjacent normal follicular epithelium (BSP: 87.88%, 55.00%, and 42.50%, respectively; OPN: 83.33%, 70.00% and 50.00%, respectively). There was a significant difference in the immunohistochemical score (IHS) for BSP and OPN protein staining between PTC specimens with and without calcification (P < 0.05). The level of BSP protein staining was found to be significantly correlated with the level of OPN protein staining in PTC specimens. We conclude that the strong correlation between BSP and OPN and PTC suggests a role for BSP and OPN in calcification and tumor progression of PTC. BSP and OPN might be useful tumour markers for the diagnosis of PTC with limited value, because both of them had low specificity.     

Macrophage‐derived osteopontin induces reactive astrocyte polarization and promotes re‐establishment of the blood brain barrier after ischemic stroke

Infarcted regions of the brain after stroke are segregated from the intact brain by scar tissue comprising both fibrous and glial components. The extent and quality of scarring is influenced by inflammation. The matricellular glycoprotein osteopontin (OPN) is strongly induced in myeloid cells after stroke and may contribute to repair of ischemic brain lesions. To elucidate the role of OPN in scar formation, we induced photothrombotic brain infarction, characterized by circumscribed cortical infarctions with a well‐defined border zone toward the intact brain parenchyma. The cellular source and functional role of OPN was addressed by studies in OPN null (OPN^‐/‐) mice, wild‐type mice depleted of hematogenous monocytes/macrophages by clodronate‐filled liposome treatment, and CCR2^‐/‐ bone marrow chimeric mice characterized by impaired hematogenous macrophage influx into the infarctions. OPN was mainly produced by hematogenous macrophages infiltrating into the inner border zone of the infarcts whereas astrocyte activation occurred in the outer border zone. In OPN^‐/‐ as well as macrophage‐depleted mice, reactive astrocytes failed to properly extend processes from the periphery toward the center of the infarctions. This was associated with incomplete coverage of neovessels by astrocytic endfeet and persistent leakiness of the damaged blood brain barrier. In conclusion, OPN produced by hematogenous macrophages induces astrocyte process extension toward the infarct border zone, which may contribute to repair of the ischemic neurovascular unit. GLIA 2015;63:2198–2207     

A case of intraductal tubulopapillary neoplasm of pancreas with severe calcification,a potential pitfall in diagnostic imaging

We experienced a case of intraductal tubulopapillary neoplasms (ITPN) of the pancreas with severe calcification, which complicated image diagnosis. A pancreas head tumor was detected in a Japanese female in her 50s. Early enhancement by contrast‐enhanced CT and coarse calcification suggested a neuroendocrine tumor, although the obstruction and dilation of the main pancreatic duct appeared to be an intraductal tumor. An endoscopic ultrasound‐guided fine needle aspiration biopsy specimen revealed adenocarcinoma tissue. Pancreaticoduodenectomy was performed, and the patient has been well without evidence of recurrence for over 10 months. Pathological examination on the resected specimen revealed that the tumor showed papillary and tubulo‐cribriform growth patterns. Together with typical immunohistochemical results, the final diagnosis of ITPN was made. Characteristically, this case showed extensive calcification of both psammoma body‐type and non psammoma body‐type with foamy macrophage aggregation. This is the first report of ITPN with two types of calcification and macrophage. Since calcification might be one of the characteristic histological findings in ITPN as shown in our case, the possibility of ITPN should be also considered when calcification is detected in pancreatic lesions by various imaging modalities.     

Wogonin suppresses osteopontin expression in adipocytes by activating PPARα

Aim:

Wogonin (5,7-dihydroxy-8-methoxyflavone), a major bioactive compound of the flavonoid family, is commonly extracted from the traditional Chinese medicine Scutellaria baicalensis and possesses antioxidant and anti-inflammatory activities and is assumed to have anti-diabetes function. Indeed, a current study has shown that it can possibly treat metabolic disorders such as those found in db/db mice. However, the underlying molecular mechanism remains largely unclear. The aim of this study was to investigate the impact of wogonin on osteopontin (OPN) expression in adipose tissue from type 1 diabetic mice and in 3T3-L1 adipocytes.

Methods:

Type 1 diabetes was induced by streptozotocin (STZ) injection. 3T3-L1 preadipocytes were converted to 3T3-L1 adipocytes through treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IBMX). Western blot analysis and RT-PCR were performed to detect protein expression and mRNA levels, respectively.

Results:

Wogonin treatment suppressed the increase in serum OPN levels and reduced OPN expression in adipose tissue from STZ-induced type 1 diabetic mice. Administration of wogonin enhanced PPARα expression and activity. Silencing of PPARα diminished the inhibitory effects of wogonin on OPN expression in 3T3-L1 adipocytes. Furthermore, the levels of c-Fos and phosphorylated c-Jun were reduced in wogonin-treated adipose tissue and 3T3-L1 adipocytes. In addition, wogonin treatment dramatically mitigated p38 MAPK phosphorylation. Pharmacological inhibition of p38 MAPK by its specific inhibitor SB203580 increased PPARα activity and decreased OPN expression.

Conclusion:

Our results suggest that wogonin downregulated OPN expression in adipocytes through the inhibition of p38 MAPK and the sequential activation of the PPARα pathway. Given the adverse effects of high OPN levels on metabolism, our results provide evidence for the potential administration of wogonin as a treatment for diabetes.     

Microdensitometry of osteopontin as an immunohistochemical prognostic biomarker in colorectal carcinoma tissue microarrays: potential and limitations of the method in ‘biomarker pathology’

Prall F, Maletzki C & Linnebacher M
(2012) Histopathology  61, 823–832 Microdensitometry of osteopontin as an immunohistochemical prognostic biomarker in colorectal carcinoma tissue microarrays: potential and limitations of the method in ‘biomarker pathology’ Aims: To explore the potential and limitations of ‘biomarker pathology’ with quantitative immunohistochemistry on tissue microarrays, taking osteopontin and colorectal carcinoma as a model system. Methods and results: Microdensitometry for quantitative evaluation of osteopontin immunohistochemistry (clone OP3N) on digital microphotographs using the public domain software ImageJ was observed to be straightforward to perform and reliable. However, using colorectal carcinoma cell lines (n = 11) the correlation between densitometric evaluations of Western blots and microdensitometry of immunocytochemistry of slide cultures was only moderate. A virtual resampling method to simulate tissue microarrays showed that, due to heterogeneity of immunostaining, tumours were misclassified in nearly 20% of the arrays, even if four punches were used. With regard to prognosis, microdensitometric evaluation of a tissue microarray made of a clinicopathologically well‐characterized series of colorectal carcinomas with long‐term follow‐up (222 cases evaluable in the tissue microarray, UICC Stages I–III/R0) showed a moderate survival advantage of patients with high osteopontin expression by microdensitometry. Conclusions: These results challenge the basic assumption that microdensitometry is a precise technique for the quantification of proteins detected by immunohistochemistry and delineate drawbacks encountered when working with tissue microarrays in clinicopathological studies.