Expression of ectonucleotide pyrophosphatase-1 in end-plate chondrocytes with transforming growth factor beta 1 siRNA interference by cyclic mechanical tension

Background Ectonucleotide pyrophosphatase/phosphodiesterase （ENPP）-I is a membrane-bound protein that catalyzes the hydrolysis of extracellular nucleoside triphosphates to monophosphate and extracellular inorganic pyrophosphate （ePPi）. Mechanical stimulation regulates ENPP-1 expression. This study sought to investigate the changes in ENPP-1 expression after stimulation using cyclic mechanical tension （CMT）.

Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis

Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate （Pi） to mineral inhibitor pyrophosphate （PPi）, where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase （TNAP） and ectonucleotide pyrophosphatase/phosphodiesterase 1 （NPP1）. The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enppl null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enppl gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected.

ENPP1/PC-1 Gene K121Q Polymorphism Is Associated with Obesity in European Adult Populations: Evidence from A Meta-Analysis Involving 24 324 Subjects

Objective Findings from the previous studies have suggested a relationship between ectonucleotide pyrophosphatase /phosphodiesterase 1 （ENPP‐1） or plasma cell membrane glycoprotein 1 （PC‐1） gene single nucleotide polymorphism （K121Q, rs1044498） and genetic susceptibility to obesity. However, such relationship is not reproduced by some currently available studies. In this context, the present study is aimed to quantitatively analyze the association of K121Q variant with obesity in all published case‐control studies in European adult populations. Methods Published literature from PubMed, EMBASE, and ISI web of science databases were retrieved. The studies evaluating the association of ENPP1/PC1 gene K121Q polymorphism with obesity were included, in which sufficient data were presented to calculate the odds ratio （OR） with 95% confidence intervals （CIs）. Results Ten case‐control studies meeting the inclusion criteria identified a total of 24,324 subjects including 11,372 obese and 12,952 control subjects. The meta‐analysis results showed a statistically significant association of K121Q with obesity [OR （95%CI）： 1.25 （1.04‐1.52） P=0.021] under a recessive model of inheritance （QQ vs. KK＋KQ） without heterogeneity or publication bias. Conclusions The results from the present study have indicated that ENPP1/PC1 Q121 variant may increase the risk of obesity and that more well‐designed studies based on a larger population will be required to further evaluate the role of ENPP1/PC1 gene K121Q polymorphism in obesity and other related metabolic syndromes.

Reductive lipid nanoparticles loaded with vinorelbine inhibit chemotherapy-induced invasion of cancer cells by modulating ENPP2

Cancer is a predominant culprit behind worldwide death and accounts for up to 10 million deaths every year.Chemotherapy is the primary therapeutic method employed for cancer in clinical settings and is essential in controlling tumor progression.Despite the advances in this field,tumor invasion and metastasis during treatment remain a significant cause of treatment failure.Nevertheless,the underlying mechanisms involving such a disappointing phenomenon are still not fully elucidated.Vinorelbine(VNB)extends the lifespan of many cancer patients in the clinic as an emerging chemotherapy drug approved by Food and Drug Administration(FDA).However,VNB-induced tumor metastasis is still an intractable problem,which may be closely related to the abnormal oxidative stress generated during VNB-mediated treatment.Hence,the study aims to construct a reductive nanosystem loaded with VNB,called VNB-VNP,to improve cancer cure rates and reduce tumor metastasis.With the reductive component vitamin E,VNB-VNP can effectively reduce oxidative stress and significantly outperform free VNB in preventing tumor progression.The transcriptome analysis shows that VNB-VNP can alleviate the over-expression of ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2),which may be the main reason why VNB-VNP can inhibit tumor invasion and metastasis.Overall,the research designs a new platform for VNB treatment,which demonstrates promising efficacy in inhibiting neoplastic progression and identifies a new mechanism associated with VNB-induced tumor metastasis,which may offer several valuable references for enhancing chemotherapy efficacy in clinical anti-tumor therapy.