Increase of Osteopontin Plasma Concentrations After Bariatric Surgery Independent from Inflammation and Insulin Resistance

Background  Osteopontin (OPN) is a multifunctional matrix glycoprotein associated with bone metabolism and has been linked to chronic inflammation, insulin resistance, and atherosclerosis. Diet-induced weight loss decreases elevated OPN concentrations in obese patients. The aim of the current study was to investigate the role of OPN after bariatric surgery, where not only improvements of chronic inflammation, insulin resistance and comorbidities, but also malabsorption and altered bone metabolism have been reported. Methods  OPN plasma concentrations were determined in 31 morbidly obese patients (5 men, 26 women, BMI 46.2 ± 7.1 kg/m², age 41 ± 11 years; mean ± SD) before and 18 months after bariatric surgery, together with parameters of bone metabolism and inflammation. Results  OPN concentrations increased by +20.3 ± 26.6 ng/ml (mean ± SD, p < 0.01), concomitant to a weight loss of −38 ± 22 kg, and a decrease in BMI by −13.1 ± 7.7 kg/m² (both p < 0.01). HOMA-index improved from 5.2 ± 3.4 to 1.5 ± 1.0 (p < 0.01). Calcium concentrations slightly decreased, and phosphate increased (−0.06 ± 0.13 mmol/l and +0.08 ± 0.16 mmol/l, respectively; both p < 0.05), while 25-OH-VitaminD₃ remained unchanged and PTH tended to increase (+5.1 ± 14.0 pg/ml, p = 0.054). Monocyte chemoattractant protein 1 and interleukin 18 were significantly decreased and associated with HOMA both before and after bariatric surgery. ΔOPN was correlated with ΔPTH, but not with other parameters. Conclusions  OPN plasma concentrations increased concomitant to weight loss after bariatric surgery, which was independent from an improvement of insulin sensitivity and a decrease of inflammatory markers. Further studies are needed to differentiate whether these changes in bone metabolism after bariatric surgery are secondary to calcium deficiency or an adaptation to weight loss. This work has been submitted in abstract form and will be in part presented at the American Diabetes Association 68th Scientific Sessions 2008, June 6th–10th, San Francisco, CA, USA.     

Osteopontin promoter polymorphisms at locus -443 are associated with metastasis and poor prognosis of human intrahepatic cholangiocarcinoma in Chinese population

Purpose: Osteopontin (OPN) is known to be a secreted adhesive glycoprotein. Role of OPN in human intrahepatic cholangiocarcinoma (ICC) has not been well understood. This study explored whether genetic variations in the osteopontin gene are associated with ICC risk, progression and metastasis. Material and methods: 260 patients with stages I to IV between 2008 and 2013 were recruited in this study and same number healthy persons were used as control. OPN-66 T/G, -156 G/GG and -443 C/T variants were genotyped using DNA from blood lymphocytes. Chi-square test and a Fisher’s exact test were used to analyze the genotype distribution between healthy subjects and patients, and further its distribution among TNM stages and incidence metastasis in patients. Results: For the variant at nt- 443 (CC), there was a significant difference between the number of patients with stage IV and those with all other stages of ICC (P < 0.01). Patients with -443 (CC) variant had significant higher incidence of lymph and distant metastasis development compared to other genotypes. For the variant at nt- 443 (CT), there was a significant difference between the number of ICC patients with stage III + IV and those with stage I + II (P < 0.01). The survival rates for ICC patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T). Conclusion: OPN -443 C/T polymorphism is a potential predictive marker of metastasis and poor prognosis in ICC patients.     

Osteopontin has a protective role in prostate tumor development in mice

Osteopontin (OPN) is a protein, generally considered to play a pro‐tumorigenic role, whereas several reports have demonstrated the anti‐tumorigenic function of OPN during tumor development. These opposing anti‐ and pro‐tumorigenic functions are not fully understood. Here, we report that host‐derived OPN plays an anti‐tumorigenic role in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model and a TRAMP tumor transplant model. Tumor suppression mediated by OPN in Rag2^?/? mice suggests that OPN is dispensable in the adaptive immune response. We found that host‐derived OPN enhanced infiltration of natural killer (NK) cells into TRAMP tumors. The requirement of OPN in NK cell migration towards TRAMP cells was confirmed by an ex vivo cell migration assay. In contrast to TRAMP cells, in vivo B16 tumor development was not inhibited by OPN, and B16 tumors did not show OPN‐mediated cell recruitment. It is possible that low levels of chemokine expression by B16 cells do not allow OPN to enhance immune cell recruitment. In addition to demonstrating the anti‐tumorigenic role of OPN in TRAMP tumor development, this study also suggests that the contribution of OPN to tumor development depends on the type of tumor as well as the source and isoform of OPN.     

The development of the pathophysiological concept of calciphylaxis in experiment and clinic

An attempt to clarify some pathophysiological aspects of calciphylaxis from both experimental and clinical points of view is presented. Until now, we cannot explain precisely various forms of calcification, affecting either soft tissues or biomaterial as well, only on the basis of metastatic or dystrophic calcification including the pure topical, local aspects. Therefore, the biological phenomenon of calciphylaxis can be useful in searching the ways for the inhibition of soft tissues and biomaterial calcification. The experiments with experimental progeria have also made it possible to study the so-called reversed calciphylaxis. The systemic reversed calciphylaxis, or ‘anacalciphylaxis’ was shown in the authors experiments with the total artificial heart as a very effective factor in the inhibition of mineralization of the TAH driving diaphragms. The discovery of the ubiquitous organ regulator of calcification, osteopontin, can greatly contribute to further elucidation of the calciphylactic mechanisms in general, and also to the prevention of calcifying lesions. It is pointed to some clinical states, predominantly the end-stage renal disease with hemodialysation where many authors pay attention to calciphylaxis as a clinical entity in a series of such cases. Calciphylaxis has been described in dermatology, nephrology and other clinical disciplines. In the area of attempts to prevent the ectopic organ calcification and also mineralization of biomaterials, a vast field of stimulation of endogenic inhibitors of calcification remains open.     

狼疮肾炎患者尿蛋白通过p38丝裂素活化蛋白激酶信号途径刺激近端肾小管上皮细胞上调表达骨调素

目的探讨p38丝裂素活化蛋白激酶(MAPK)信号通路在狼疮肾炎(LN)尿蛋白介导近端肾小管上皮细胞(HK-2)表达骨调素(DPN)中的作用。方法收集狼疮肾炎患者24h的尿液提纯总蛋白，体外刺激HK-2细胞，分别用逆转录-聚合酶链式反应(RT-PCR)和Western印迹法观察应用p38MAPK特异性阻断剂SB203580对。HK-2细胞表达OPN mRNA及蛋白的影响：免疫荧光法检测OPN及其受体CD44在细胞中的表达。结果狼疮肾炎患者尿蛋白可刺激HK-2细胞OPN mRNA及蛋白上调表达，并呈时间和浓度依赖性，而SB203580可明显抑制这一作用。结论狼疮肾炎尿蛋白可通过p38MAPK途径刺激HK-2细胞OPN mRNA和蛋白上调表达。     

Biodegradable gelatin microspheres enhance the neuroprotective potency of osteopontin via quick and sustained release in the post-ischemic brain

Gelatin microspheres (GMSs) are widely used as drug carriers owing to their excellent biocompatibilities and toxicologically safe degradation products. The drug release profile is easily tailored by controlling the cross-linking density and surface-to-volume ratio, i.e. size, of the GMS. In this study, we employed GMSs which are 25 μm in diameter and cross-linked with 0.03125% glutaraldehyde, to enable rapid initial and a subsequent sustained release. Therapeutic potency of human recombinant osteopontin (rhOPN) with or without encapsulation into GMSs was investigated after administrating them to rat stroke model (Sprague–Dawley; middle cerebral artery occlusion, MCAO). The administration of rhOPN/GMS (100 ng/100 μg) at 1 h post-MCAO reduced the mean infarct volume by 81.8% of that of the untreated MCAO control and extended the therapeutic window at least to 12 h post-MCAO, demonstrating a markedly enhanced therapeutic potency for the use of OPN in the post-ischemic brain. Scanning electron microscopy micrographs revealed that GMSs maintained the three-dimensional shape for more than 5 days in normal brain but were degraded rapidly in the post-ischemic brain, presumably due to high levels of gelatinase induction. After encapsulation with GMS, the duration of OPN release was markedly extended; from the period of 2 days to 5 days in normal brain, and from 2 days to 4 days in the post-ischemic brain; these encompass the critical period for recovery processes, such as vascularization, and controlling inflammation. Together, these results indicate that GMS-mediated drug delivery has huge potential when it was used in the hyperacute period in the post-ischemic brain.     

Prognostic value of osteopontin expression in esophageal squamous cell carcinoma: A meta-analysis

ObjectiveTo explore the prognostic role of osteopontin (OPN) overexpression in esophageal squamous cell carcinoma (ESCC).MethodsThe PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Data (CBM) and VIP databases were searched from the establishment dates of the databases to March 31, 2019, for potentially related studies. Stata 12.0 software was used for statistical analyses, and the hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the correlation of OPN overexpression with the overall survival (OS) and progression-free survival (PFS) of ESCC patients.ResultsA total of 8 studies involving 811 patients from China or Japan were included. OPN overexpression was demonstrated to be significantly associated with poor OS (HR = 1.86, 95% CI: 1.22–2.83, P = 0.004), with high heterogeneity (I² = 61.2%, P = 0.012), and poor PFS (HR=1.63, 95% CI: 1.08–2.47, P = 0.020), without heterogeneity (I² = 0.0%, P = 0.839). Subgroup analysis results were similar to the pooled results.ConclusionOPN overexpression might serve as a promising independent prognostic risk factor in Chinese and Japanese ESCC patients. However, more well-designed studies enrolling more patients are still needed to verify our findings.     

子痫前期患者胎盘骨桥蛋白及整合素ανβ3的表达及意义

目的探讨骨桥蛋白（OPN）及其受体整合素ανβ3在子痫前期（preeclampsia,PE）患者胎盘组织中的表达及其意义。方法2008年11月-2009年9月,采用免疫组织化学方法检测20例PE患者（轻度及重度PE各10例）和14例正常足月孕妇（对照组）胎盘组织中OPN及ανβ3蛋白表达水平。采用RT-PCR检测各组孕妇胎盘组织中的OPN、αν和β3的mRNA的表达水平。结果PE组孕妇胎盘组织中OPN及ανβ3蛋白表达低下,与对照组相比,差异有统计学意义（P〈0.05）;重度PE组OPN及ανβ3蛋白表达水平更低,与轻度PE组比较,差异有统计学意义（P〈0.05）。PE组孕妇胎盘组织中OPNmRNA水平明显低于对照组,两组差异有统计学意义（P〈0.05）;重度PE组OPNmRNA水平显著降低,与轻度PE组比较,两组差异有统计学意义（P〈0.05）;但αν和β3mRNA的表达水平三组间比较差异无统计学意义。结论OPN及其受体整合素ανβ3在PE胎盘组织中的低表达可能在子痫前期的发病过程中起重要作用。     

Evaluation of IGFBP5 expression and plasma osteopontin level in COVID-19 patients

PurposeThe aim of this study is to investigate insulin-like growth factor binding protein 5 (IGFBP5) expression in coronavirus disease 2019 (COVID-19) patients and its relationships with COVID-19 laboratory findings and plasma osteopontin (OPN) levels.Materials and methodsWe enrolled 60 patients with COVID-19 and 30 healthy individuals in this study. mRNA expression of IGFBP5 was measured by RT-PCR. Plasma OPN levels were measured via the ELISA method.ResultsPlasma OPN levels were higher and IGFBP5 expression levels were lower in COVID-19 patients than in the healthy individuals (p ?= ?0.0057 and p ?= ?0.0142, respectively). Critically ill patients had higher OPN and lower IGFBP5 than non-critically ill patients. Patients with affected lungs demonstrated increased OPN and decreased IGFBP5 (p ?= ?0.00032 and p ?= ?0.044, respectively). Receiver operating characteristic (ROC) analysis indicated that IGFBP5 expression and OPN levels can be used discriminate non-critically from critically ill patients (p ?= ?0.049; p ?= ?0.0016, respectively).ConclusionThis study demonstrated that patients with a poor prognosis had increased OPN and decreased IGFBP5. High values of OPN and low values of IGFBP5 may be considered as signs of disease severity. Tissue-specific IGFBP5 expression may contribute to understanding the role of IGFBP5 in the lungs in COVID-19 cases.