Acidic Environment Induces Pyroptosis of NLRP3 Inflammatory Vesicle-Mediated Nucleus Pulposus Cells Through Up-Regulation of POSTN Expression

SUMMARY: Intervertebral disc degeneration (IVDD) is induced by nucleus pulposus (NP) dysfunction as a result of massive loss of NP cells. It has been reported that the acidic microenvironment of the intervertebral disc (IVD) can induce NP cell pyroptosis, and that up-regulation of periostin (POSTN) expression has a negative effect on NP cell survival. However, the relationship between the acidic environment, POSTN expression level and NP cell pyroptosis is unclear. Therefore, the aim of this study was to explore the relationship between acidic environment and POSTN expression level in NP cells, as well as the effect of POSTN in acidic environment on NP cell pyroptosis. NP cells were obtained from the lumbar vertebrae of Sprague Dawley (SD) male rats. These cells were divided into normal and acidic groups according to whether they were exposed to 6 mM lactic acid solution. And NP cells in the acidic group were additionally divided into three groups: (1) Blank group: no transfection; (2) NC group: cells transfected with empty vector plasmid; (3) sh-POSTN group: cells transfected with sh-POSTN plasmid to knock down the expression level of POSTN. Quantitative real-time PCR (qRT-PCR) and western blot was performed to assess the expression of POSTN at the mRNAand protein levels. CCK8 was used to evaluate cell survival. Western blot, in addition, was performed to examine acid-sensing ion channels (ASIC)-related proteins. And pyroptosis was detected by ELISA and western blot. The expression level of POSTN was significantly increased in NP cells in acidic environment. Knockdown of POSTN expression promoted the survival of NP cells in acidic environment and reduced the protein levels of ASIC3 and ASIC1a in NP cells. Moreover, knockdown of POSTN expression decreased the pyroptosis proportion of NP cells and the levels of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. The levels of pyroptosis-related proteins NLRP3, ASC, cleaved-Caspase-1, and cleaved-GSDMD were also affected by the decreased POSTN expression. The extracellular acidic environment created by lactic acid solution activated NLRP3 inflammatory vesicle-induced caspase-1 to get involved in NP cell pyroptosis by up-regulating POSTN expression.

La degeneración del disco intervertebral (DDIV) es inducida por una disfunción del núcleo pulposo (NP) como resultado de una pérdida masiva de células NP. Se ha informado que el microambiente ácido del disco intervertebral (DIV) puede inducir la piroptosis de las células NP y que la regulación positiva de la expresión de periostina (POSTN) tiene un efecto negativo en la supervivencia de las células NP. Sin embargo, la relación entre el ambiente ácido, el nivel de expresión de POSTN y la piroptosis de las células NP es poco clara. Por lo tanto, el objetivo de este estudio fue explorar la relación entre el ambiente ácido y el nivel de expresión de POSTN en células NP, así como el efecto de POSTN en ambiente ácido sobre la piroptosis de las células NP. Las células NP se obtuvieron de las vertebras lumbares de ratas macho Sprague Dawley (SD). Estas células se dividieron en grupos normales y ácidos según se expusieron a una solución de ácido láctico 6 mM. Las células NP en el grupo ácido se dividieron adicionalmente en tres grupos: (1) Grupo en blanco: sin transfección; (2) grupo NC: células transfectadas con plásmido vector vacío; (3) grupo sh-POSTN: células transfectadas con plásmido sh-POSTN para reducir el nivel de expresión de POSTN. Se realizó una PCR cuantitativa en tiempo real (qRT-PCR) y una transferencia Western para evaluar la expresión de POSTN en los niveles de ARNm y proteína. Se utilizó CCK8 para evaluar la supervivencia celular. Además, se realizó una transferencia Western para examinar las proteínas relacionadas con los canales iónicos sensibles al ácido (ASIC). La piroptosis se detectó mediante ELISA y Western blot. El nivel de expresión de POSTN aumentó significativamente en células NP en ambiente ácido. La eliminación de la expresión de POSTN promovió la supervivencia de las células NP en un ambiente ácido y redujo los niveles de proteína de ASIC3 y ASIC1a en las células NP. Además, la eliminación de la expresión de POSTN disminuyó la proporción de piroptosis de las células NP y los niveles de citocinas proinflamatorias interleucina (IL) - 1β e IL-18. Los niveles de proteínas relacionadas con la piroptosis NLRP3, ASC, Caspasa-1 escindida y GSDMD escindida también se vieron afectados por la disminución de la expresión de POSTN. El ambiente ácido extracelular creado por la solución de ácido láctico activó la caspasa-1 inducida por vesículas inflamatorias NLRP3 para involucrarse en la piroptosis de las células NP mediante la regulación positiva de la expresión de POSTN.

Is periostin useful as a biomarker for fibrous dysplasia? / ¿Es útil periostina como biomarcador de displasia fibrosa?

Fibrous dysplasia (FD) is an infrequent non-hereditary bone disease caused by a somatic mutation of the GNAS gene. Periostin is a novel marker that increases during tissue healing and fibrous or inflammatory diseases. We conducted an exploratory case-control study to evaluate sensitivity of periostin as a biomarker of FD. The study comprised 15 patients with FD, and healthy age- and sex-matched subjects (controls). Serum periostin levels were assessed and comparisons were established between FD patients and controls, and between patients with the monostotic and the polyostotic form of FD. No statistically significant differences in serum periostin levels were observed between the cohort of FD patients studied here and the control group (FD: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15), or between the clinical forms of FD (polyostotic: 51.8±9.1ng/ml vs. monostotic: 49.6±13 ng/ml; p=0.66). A sub-analysis performed to compare serum levels of periostin in FD patients with and without a history of fractures showed no statistically significant differences [fracture patients (n=4): 41.2±17ng/ml vs. non-fracture patients (n=11): 49.9±11 ng/ml; p=0.47].Lastly, sensitivity of periostin as a biomarker of FD was analyzed, and was found to have low sensitivity to estimate disease activity [ROC curve; cut-off points: 39.625(0.867-0.467)]. To conclude, in the cohort of FD patients studied here, periostin serum levels did not differ significantly from those of the control group or between the two forms of the disease, and showed low sensitivity as a biomarker of the disease. (AU)

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria producida por una mutación somática del gen GNAS. Periostina (Postn) es un novedoso marcador, cuyos niveles séricos se encuentran elevados en los procesos de reparación tisular, enfermedades fibrosas o inflamatorias. Llevamos a cabo un estudio exploratorio caso-control para evaluar la sensibilidad de Postn como biomarcador de DF. Se incluyeron en el estudio 15 pacientes con DF apareados por edad y género con sujetos sanos (controles) en los cuales se evaluó los niveles séricos de Postn en pacientes con DF y controles y según forma de presentación clínica. No observamos diferencias estadísticamente significativas en los niveles séricos de Postn y el grupo control (DF: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15) como así tampoco por forma clínica de DF (poliostótica: 51.8±9.1ng/ml vs. monos-tótica: 49.6±13 ng/ml; p=0.66). Posteriormente realizamos un sub-análisis para evaluar los niveles séricos de Postn en los pacientes con DF y antecedentes de fracturas no observan-do diferencias estadísticamente significativas [fracturados (n=4): 41.2±17ng/ml vs. no frac-turados (n=11): 49.9±11 ng/ml; p=0.47]. Por último analizamos la sensibilidad Postn como biomarcador de DF, mostrando este poseer escasa sensibilidad para estimar actividad de la enfermedad [curva ROC; puntos de corte: 39.625 (0.867-0.467)]. En conclusión, los ni-veles séricos de Postn en nuestra cohorte de pacientes con DF no mostraron diferencias estadísticamente significativas comparadas con el grupo control o por forma clínica de presentación, mostrando una baja sensibilidad como biomarcador de enfermedad. (AU)

Aqueous humor heat-shock protein 70, periostin, and irisin levels in patients with pseudoexfoliation syndrome / Níveis de proteína de choque térmico 70, de periostina e de irisina no humor aquoso em pacientes com pseudoexfoliação

ABSTRACT Purpose: To measure humor heat-shock protein 70, periostin, and irisin levels in patients with pseudoexfoliation syndrome and cataract (without glaucoma), and compare them with those of patients with cataract but without pseudoexfoliation. Methods: We examined 31 eyes of 31 patients with pseudoexfoliation and cataract (without glaucoma) and 30 eyes of 30 patients with cataract. We collected aqueous humor samples from all patients at the time of cataract surgery through a limbal paracentesis via a 25-gauge cannula mounted on a tuberculin syringe that received 100 to 150 µL of aqueous humor. We measured levels of aqueous humor Heat shock protein 70, periostin, and irisin using enzyme-linked immunosorbent assay methods. Results: The age (p=0.221) and gender (p=0.530) means were similar between the pseudoexfoliation and control groups. The mean Heat shock protein 70 level (29.22 ± 9.46 ng/mL; 17.88-74.46) in the pseudoexfoliation group was significantly higher than that in the control group (19.03 ± 7.05 ng/mL; 9.93-35.52; p<0.0001). The mean periostin level was significantly higher (6017.32 ± 1271.79 pg/mL; 3787.50-10803.57) in the pseu doexfoliation group than that in the control group (4073.63 ± 1422.79 pg/mL; 2110.44-7490.64; p<0.0001). The mean irisin level (53.77 ± 10.19 ng/mL; 29.46-71.16) was significantly higher than that in the control group (39.29 ± 13.58 ng/mL; 19.41-70.56; p<0.0001). Conclusions: Heat shock protein 70, periostin, and irisin levels increase in the aqueous humor of patients with pseudoexfoliation without glaucoma.

RESUMO Objetivo: Comparar os níveis de proteína de choque térmico 70, de periostina e de irisina no humor aquoso de pacientes com pseudoexfoliação com catarata sem glaucoma e compará-los com pacientes com catarata sem pseudoexfoliação. Métodos: Trinta e um olhos de 31 pacientes com pseudoexfoliação com catarata sem glaucoma e 30 olhos de 30 indivíduos com catarata foram incluídos neste estudo. Amostras de humor aquoso foram coletadas de todos os pacientes no momento da cirurgia de catarata e obtidas através de uma paracentese límbica por meio de uma cânula de calibre 25 acoplada a uma seringa com tuberculina. Foram coletados 100 a 150 µL de humor aquoso. Os níveis de proteína de choque térmico 70, de periostina e de irisina no humor aquoso foram medidos usando o método de ensaio imunossorvente ligado a enzima. Resultados: A média da idade (p=0,221) e sexo (p=0,530) foram semelhantes entre os grupos pseudoexfoliação e controle. Os níveis médios de proteína de choque térmico 70 foram 29,22 ± 9,46 ng/mL (17,88-74,46) e 19,03 ± 7,05 ng/ mL (9,93-35,52) nos grupos pseudoexfoliação e controle, respectivamente. Os níveis de proteína de choque térmico 70 foram maiores no grupo pseudoexfoliação (p<0,0001). O nível médio de periostina foi de 6017,32 ± 1271,79 pg/mL (3787,50-10803,57) no grupo pseudoexfoliação e 4073,63 ± 1422,79 pg/mL (2110,44-7490,64) no grupo controle. O nível médio de periostina também foi maior no grupo pseudoexfoliação (p<0,0001). Os níveis médios de irisina foram 53,77 ± 10,19 ng/mL (29,46-71,16) e 39,29 ± 13,58 ng/mL (19,41-70,56) nos grupos pseudoexfoliação e controle, respectivamente. O nível médio de irisina foi maior no grupo pseudoexfoliação do que no grupo controle (p<0,0001). Conclusões: Os níveis de proteína de choque térmico 70, de periostina e de irisina aumentam no humor aquoso de pacientes com pseudoexfoliação sem glaucoma.

Comparative Study Between Periostin And Osteocalcin As Biomarkers For Osteoporosis And Fracture Risk In Egyptian Postmenopausal Women

Objective: This study aimed to compare between periostin and osteocalcin as biomarkers in Egyptian postmenopausal women with osteoporosis and to explore their possible relationship with fracture risk. Methods: This study included 90 postmenopausal females recruited from Al-Hussein University Hospital, Cairo, Egypt; divided into three groups; 35 postmenopausal osteoporotic females with low fracture risk (group I), 35 postmenopausal osteoporotic females with high fracture risk (group II), and 20 apparently healthy controls. Serum periostin, osteocalcin, and estrogen were measured by Enzyme Linked Immunosorbent Assay (ELISA). Fracture risk assessment was calculated. Alkaline phosphatase (ALP), total and ionized calcium, Aspartate transaminase (AST), and Alanine transaminase (ALT) were measured spectrophotometrically. Results: The diagnostic performance of periostin for discriminating high fracture risk from low fracture risk groups showed the specificity of (68.6 %) and sensitivity of (100 %), while for osteocalcin the specificity was (51.4 %) and the sensitivity was (68.6 %) respectively. Moreover, the multi Receiver Operating Characteristics (multi-ROC) curve for periostin and osteocalcin together revealed improved specificity and sensitivity of (100 %) each. Conclusion: Periostin was superior to osteocalcin in discriminating high fracture risk from low fracture risk postmenopausal osteoporotic groups. Moreover, dual use of both markers gave the highest discriminative power between low and high fracture risk groups with 100 % specificity and sensitivity.

Serum Periostin Level in Asthmatic Children with Exercise Induced Bronchospasm

Background:There are few biomarkers that can be easily accessed in clinical settings and may reflect refractory Th2-eosinophlic inflammation and remodeling of the asthmatic airways. Serum periostin may be one such biomarker to aid our understanding of the patho-bio-physiology of asthma and exercise induced asthma. The aim of the study is to explore the relationship between serum periostin level and exercise induced bronchoconstriction in asthmatic children.Materials and Methods: This cross-sectional study was carried out on (90) children both sexes aged from 6 to 15 years including, (60) children with bronchial asthma and (30) children were enrolled as control group in the period from January 2018 to January 2019. Patients were randomly classified into two groups: I) Patient group: divided into 2 groups according to standardized treadmill exercise challenge test: Group A: (30) asthmatic children with positive test. Group B: (30) asthmatic children with negative test. II-Control group: (30) children apparently healthy with no personal or family history of asthma. All children were subjected to the following Investigations: Chest x-ray, pulmonary functions tests (FEV1& PEFR) except controls, Laboratory investigations as CBC and Serum periostin level Results:The mean values of both the percentage of PEFR and FEV1 after exercise in group A were significantly lower than those in group B and the percentage of PEFR and FEV1after exercise in each group were significantly lower than the percentage before exercise in the same group. The mean value of eosinophilic count in group A was significantly higher than (group B and control group) and the mean value of eosinophilic countin group B was significantly higher than control group. The mean value of serum level of periostin in group A was significantly higher than (group B and control group), however, there was no significant difference between group B and control group as regard to serum level of periostin.Chest tightness, cough and wheezes after exercise and eosinophilic count in patients with high serum periostin level were significantly higher than patients with low serum periostin level, and both PEFR and FEV1after exercise in patients with high serum periostin level were significantly lower than patients with low serum periostin level. Also the normal serum periostin levels vary among different age groups.Conclusion:Serum periostin level can be considered as a useful biomarker for diagnosis of Exercise induced bronchospasm (EIB) in asthmatic children especially when lung function test cannot be done However, cautious is required in evaluating serum periostin levels in children because it varies with age.

Dynamic changes of periostin and collagen I in the sclera during progressive myopia in guinea pigs / Alterações dinâmicas de periostina e colágeno I na esclera durante miopia progressiva em cobaias

ABSTRACT Purpose: To investigate periostin and collagen I expression during a scleral remodeling in myopic eyes and to determine their role in collagen remodeling of the myopic sclera. Methods: Fifty one-week-old guinea pigs were divided into the control and form-deprivation myopia (FDM) groups. The eyes of animals in the form-deprivation myopia group were covered for 2, 4, and 8 weeks, or were covered for 4 weeks and then uncovered for 2 weeks. The diopters and axial lengths in the eyes in each group of guinea pigs were measured. Immunohistochemistry and reverse transcription polymerase chain reaction were used to detect the relative protein and mRNA expressions of periostin and collagen I in the scleral tissues of guinea pig. Results: Before masking, guinea pigs in the control and form-deprivation myopia groups were hypermetropic and did not differ significantly (p>0.05). Hypermetropic refraction in the control group gradually decreased. In guinea pigs from the form-deprivation myopia group, the refractive power gradually changed from +2.14 ± 0.33 D to -7.22 ± 0.51 D, and the axial length gradually changed from 5.92 ± 0.37 mm to 8.05 ± 0.34 mm from before until the end of masking. Before covering, no significant difference was observed in the relative collagen I and periostin mRNA and protein expression levels in the sclera of the guinea pig control and form-deprivation myopia groups (p>0.05). The relative collagen I and periostin protein and mRNA expression levels in the sclera of guinea pigs in the form-deprivation myopia group at 2, 4, and 8 weeks, and after covering the eyes for 4 weeks followed by uncovering for 2 weeks, were significantly lower than those in the control group (p<0.05). The collagen I and periostin mRNA expression levels were positively correlated with protein expression levels in the sclera of guinea pigs (protein: r=0.936, p<0.05; mRNA: r=0.909, p<0.05). Conclusions: Periostin was expressed in the myopic sclera of guinea pigs, and changes in periostin and collagen I expression were highly consistent. Periostin and collagen I may be involved in the regulation of scleral remodeling in myopia.

RESUMO Objetivo: Investigar a expressão da periostina e do colágeno I durante o remodelamento escleral em olhos míopes e determinar seu papel na remodelação do colágeno da esclera miópica. Métodos: Cinquenta cobaias com uma semana de idade foram divididas em grupo controle e miopia de privação de forma. Os olhos dos animais no grupo de miopia de privação de forma foram cobertos por 2, 4 e 8 semanas, ou foram cobertos por 4 semanas e depois descobertas por 2 semanas. As dioptrias e comprimentos axiais dos olhos em cada grupo de cobaias foram medidos. A imunohistoquímica e a reação em cadeia da polimerase com transcrição reversa foram utilizadas para detectar as expressões relativas de proteína e mRNA de periostina e colágeno I em tecidos esclerais das cobaias. Resultados: Antes do mascaramento, as cobaias nos grupos controle e miopia de privação de forma eram hipermetrópicas e não diferiam significativamente (p>0,05). A refração hipermetrópica no grupo controle diminuiu gradualmente. Nas cobaias do grupo de miopia de privação de forma, a potência de refração mudou gradualmente de +2,14 ± 0,33 D para -7,22 ± 0,51 D e o comprimento axial mudou gradualmente de 5,92 ± 0,37 mm para 8,05 ± 0,34 mm desde antes até o final do mascaramento. Antes do mascaramento, nenhuma diferença significativa foi observada nos níveis de expressão de mRNA e proteína de colágeno I e periostina na esclera dos grupos controle e miopia de privação de forma (p>0,05). Os níveis relativos de expressão de colágeno I e proteína periostina e mRNA na esclera de cobaias no grupo de miopia de privação de forma em 2, 4 e 8 semanas, e após cobertura dos olhos por 4 semanas seguido de descoberta por 2 semanas, foram significativamente menores que aqueles no grupo controle (p<0,05). Os níveis de expressão de mRNA, colágeno I e proteína periostina foram positivamente correlacionados com os níveis de expressão de proteína na esclera das cobaias (proteína: r=0,936, p<0,05; mRNA: r=0,909, p<0,05). Conclusões: A periostina foi expressa na esclerótica míope de cobaias e as alterações na expressão de periostina e colágeno I foram altamente consistentes. A periostina e o colágeno I podem estar envolvidos na regulação do remodelamento escleral na miopia.

Periostin inhibits hypoxia-induced oxidative stress and apoptosis in human periodontal ligament fibroblasts p38 MAPK signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of periostin on hypoxia-induced oxidative stress and apoptosis in human periodontal ligament fibroblasts and the molecular mechanism involved.@*METHODS@# cultured human periodontal ligament fibroblasts were placed in an anaerobic gas-producing bag for hypoxia treatment for 48 h followed by treatment with periostin at low (25 ng/mL), moderate (50 ng/mL) or high (100 ng/mL) doses. MTT assay was used to measure the cell viability, and the cell apoptosis rate was determined using flow cytometry. The contents of IL-1β, IL-6 and TNF-α in the cells were determined with ELISA, and ROS levels were measured using a fluorescent plate reader. The intracellular SOD activity was detected using ELISA. The expressions of HIF-1α, P21, cyclin D1, Bax, cleaved caspase-3, Bcl-2, P38MAPK and p-p38 MAPK proteins in the cells were detected with Western blotting.@*RESULTS@#Hypoxia treatment significantly reduced the cell viability ( < 0.05), increased P21, Bax, and cleaved caspase-3 protein levels ( < 0.05), promoted cell apoptosis ( < 0.05), and decreased cyclin D1 and Bcl-2 protein levels ( < 0.05) in the cells. Compared with the hypoxic group, the cells treated with periostin at different concentrations showed significantly increased cell viability ( < 0.05) with significantly lowered apoptotic rates ( < 0.05) and decreased expression levels of Bax and cleaved caspase-3 ( < 0.05) but significantly increased expression levels of cyclin D1 and Bcl-2 ( < 0.05). Hypoxic exposure of the cells resulted in significantly increased expression levels of HIF-1α and p-p38 MAPK ( < 0.05) and increased levels of IL-1β, IL-6, TNF-α and ROS ( < 0.05) but decreased SOD activity ( < 0.05). Periostin treatment at different concentrations significantly lowered the expression levels of HIF-1α and p-p38 MAPK ( < 0.05) and the levels of IL-1β, IL-6, TNF-α and ROS ( < 0.05) and significantly increased SOD activity in the hypoxic cells ( < 0.05).@*CONCLUSIONS@#Periostin promotes the proliferation, inhibits apoptosis, enhances cellular antioxidant capacity, and reduces inflammatory damage in human periodontal ligament fibroblasts exposed to hypoxia possibly by inhibiting the activation of the p38 MAPK signaling pathway.

Periostin regulated by let-7/miR-98 family mediates the apoptosis and epithelial-mesenchymal transition of colon cancer / 中华肿瘤杂志

Objective@#To observe the expressions of periostin (Postn) in colon cancer tissues and cells, and to investigate its biological effect and mechanism in colon cancer cells.@*Methods@#Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used to detect the expressions of Postn, let-7a and miR-98 in 20 pairs of colon cancer tissues and adjacent normal tissues, colon cancer cell lines including SW480, HT-29, HCT-116 and human normal colon epithelial cell NCM460. Small interfering RNAs (siRNAs) of Postn, pcDNA3.1-Postn plasmids, let-7a mimic and its negative control let-7a mimic-NC, miR-98 mimic and its negative control miR-98 mimic-NC were transfected into HCT-116 cells. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) was used to detect cell viability. Flow cytometry was used to detect cell apoptosis. Luciferase reporter gene assay was used to determine the targeting relationship between miRNAs and Postn.@*Results@#Compared with adjacent normal tissues, Postn expression was up-regulated (P<0.05) while let-7a/miR-98 expression was down-regulated (P<0.05) in colon cancer tissues. Compared with NCM460 cells, Postn expression was up-regulated (P<0.05) while let-7a/miR-98 expression was down-regulated (P<0.05) in SW480, HT-29 and HCT-116 cells. In colon cancer tissues, the expression of Postn was negatively correlated with the expressions of let-7a and miR-98 (r=-0.69, P<0.001; r=-0.80, P<0.001). Inhibition of Postn in vitro reduced the viability of HCT-116 cells [(53.73±7.63)%, P<0.05], increased the apoptotic rate [(22.88±3.40)%, P<0.05], enhanced the expression of epithelial-mesenchymal transition (EMT) marker E-cadherin (2.44±0.39, P<0.05), while down-regulated the expressions of N-cadherin and Vimentin (0.44±0.07 and 0.38±0.06, P<0.05). Overexpression of Postn in vitro enhanced the cell viability of HCT-116 cells [(134.41±8.82) %, P<0.05], decreased the expression of E-cadherin (0.55±0.09, P<0.05), increased the expressions of N-cadherin and Vimentin (2.93±0.42 and 2.24±0.34, P<0.05), but had no effect on the apoptotic rate (P>0.05). Overexpression of let-7a or miR-98 partially reversed the biological effects of Postn overexpression in colon cancer cells, which implicated that Postn was a target gene of let-7a/miR-98.@*Conclusions@#Postn is a cancer-promoting molecule of colon cancer, and inhibition of Postn expression can increase the apoptotic rate of colon cancer cells and repress EMT. Postn expression and function is regulated by let-7a/miR-98.

Effects of periostin on hepatocellular carcinoma cells invasion, metastasis and prognosis / 中华肝脏病杂志

Objective@#To investigate the prognostic relationship between the expression levels of periostin (POSTN) in hepatocellular carcinoma (HCC) tissues as well as its effect in invasion and metastasis.@*Methods@#The expression levels of POSTN in liver cancer tissues were detected with real-time quantitative PCR (QPCR) and immunohistochemistry (IHC). Kaplan-Meier method and Log-rank test were used to analyze the relationship between POSTN expression level and postoperative prognosis in patients with liver cancer. The expression of POSTN in hepatocellular carcinoma cells with different metastasis characteristics were detected in vitro and the overexpression of POSTN in low metastatic hepatocellular carcinoma cells was mediated through plasmid transfection techniques. The effects of POSTN on invasion and metastasis of hepatocellular carcinoma cells were determined by transwell migration and matrigel invasion assay. The comparative expression level of POSTN was analyzed by t-test.@*Results@#The expression levels of POSTN in tissues from high to low was in the order of metastatic liver cancer tissues, non-metastatic liver cancer tissues and normal liver tissues (P = 0.006). The median survival time and 3-year survival rate in postoperative patients with hepatocellular carcinoma of high POSTN expression level were significantly lower than the low expression group (10.00 months, 44.44%; 59.00 months, 53.13%, P = 0.031 2). In in vitro testing, the expression of POSTN was highest in MHCC97H cells with high metastatic characteristics as compared with Huh7 and MHCC97L cells with low and medium metastatic characteristics. After overexpression of POSTN in MHCC97L cells, the migration and invasion capacity of MHCC97L cells was increased.@*Conclusion@#POSTN is associated with pathological processes such as metastasis and invasion of liver cancer, which may promote the migration and invasion of liver cancer cells. It is expected to be an important prognostic biomarker of tumor recurrence and a therapeutic target for inhibiting the occurrence of metastasis in postoperative patients with hepatocellular carcinoma.

Periostin, osteopontin and asthma / 国际儿科学杂志

Both periostin and osteopontin belong to extracellular matrix proteins and have various biological functions.Especially in allergic inflammatory diseases,they were involved in different aspects of the pathogenesis of asthma,such as airway inflammation and airway remodeling.Recent studies have shown that periostin and osteopontin play an important role in the assessment and treatment of asthma as emerging biomarkers.This article will elaborate on the new developments of the relationship between periostin,osteopontin and asthma.

Experimental study of periostin promoting rapid distraction osteogenesis of the rabbit mandible / 口腔疾病防治

Objective @#To explore the promoting effect of periostin on rapid distraction osteogenesis of the rabbit mandible and provide experimental evidence for the clinical use of periostin to promote osteogenesis.@*Methods@#Twenty-four New Zealand male white rabbits underwent distraction osteogenesis, and after 3 days of retention, they were rapidly stretched at a stretch rate of 2 mm/d (total 5 d). The animals were randomly divided into group A and group B (12 per group). On the last day of the stretch, 0.5 mL of normal saline containing 40 μg of recombinant periostin was given to group B or an equal volume of normal saline was added to the control group (group A) for 8 days. At 4 weeks and 8 weeks post-stretch, 8 animals were randomly selected from each group to undergo a CT scan under general anesthesia. The bone mineral density and bone mineral content were detected by dual energy X-ray absorptiometry. Eight weeks post-stretch, all of the experimental animals were sacrificed. Six animals were randomly selected from each group for micro-CT and a histological examination, and the remaining animals were subjected to biomechanical tests. @*Results @#CT images showed that the new bone formation in the distraction space of group B was significantly better than that of group A at 4 and 8 weeks post-stretch. At 4 weeks and 8 weeks post-stretch, the bone mineral density in group B was (0.157 ± 0.016) g/cm 2 and (0.234 ± 0.023) g/cm 2, respectively, and the bone mineral content was (0.096 ± 0.010) g and (0.204 ± 0.017) g, respectively. The above four means were significantly higher in group B than in group A (P < 0.001). The micro-CT images and data suggest that the stretch gap microstructure of group B has more mature features. Histological experiments showed that the trabecular bone of group B was thick and mature, with few chondrocytes. The biomechanical test results showed that the biomechanical strength of the distraction gap in group B was (228.47 ± 39.98) N, which was 1.24 times that of group A (P = 0.045).@*Conclusion@# Interstitial use of periosteal protein in the distraction space of the mandible in rabbits can promote local new bone formation and mineralization.

Expression of periostin in gingival tissue of patients with chronic periodontitis and its clinical significance / 吉林大学学报(医学版)

Objective: To detect the expressions of periostin, matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in gingival tissue of the patients with chronic periodontitis, and to explore the possible role of periostin in the occurrence and development of chronic periodontitis and its related biological mechanism. Methods: A total of 23 normal gingival tissues (control group) and 19 inflammatory gingival tissues (case group) were selected. The expressions of periostin, MMP-8 and TIMP-2 in gingival tissue of the patients in two groups were detected by immunohistochemical SP method. The correlation between the expressions of periositn and MMP-8 and TIMP-2 in gingival tissue of the patients in two groups were detected by Spearman analysis. Results: The positive expression rate of periostin in gingival tissue of the patients in case group was lower than that in control group (P<0. 05). The correlative analysis results demonstrated that the expression of periostin had negative relationship with the expression of MMP-8 (r=-0.51, P<0. 05) in control group, and positive relationship with the expression of TIMP-2 (r=0. 50, P<0. 05); in case group, the expression of periostin had negative relationship with the expression of MMP-8 (r=-0.482, P<0. 05), and positive relationship with the expression of TIMP-2 (r= 0.655, P<0. 05). Conclusion: Periostin can be used as a preliminary indicator for maintaining the structural stability of gingival tissue, and become a research target for periodontal tissue regeneration.

Role of periostin in PDGF-induced proliferation and extracellular matrix accumulation of mouse mesangial cells / 中国药理学通报

;Aim To investigate the role of periostin in PDGF-induced proliferation and extracellular matrix accumulation of mouse mesangial cells. Methods The effects of PDGF on periostin protein, cell proliferation and extracellular matrix accumulation were detected. The cells were collected at 0, 2,4, 6, 12 h after stimulation with PDGF(10 (ig • L " 1 ) to detect the expression of periostin, PCNA, FN and TGF-ßl by Western blot. The silencing effect of sh-periostin vector on periostin protein in mouse mesangial cells was identified by Western blot. Cells were randomly divided into control group, PDGF group, PDGF + sh-nc group and PDGF + sh-periostin group to detect the role of periostin in PDGF-induced proliferation and extracellular matrix accumulation of mouse mesangial cells. Results PDGF could elevate periostin protein expression. Western blot result showed that periostin protein expression in PDGF-stimulated groups was significantly higher than that in Oh group, which was consistent with the result of immunofluorescence. Positive expression of periostin was located in cytoplasm. Western blot result showed that PCNA, FN and TGF-ßl protein in PDGF-stimulated groups increased as compared with Oh group. shRNA vector aimed at periostin (sh-periostin vector) could partially reverse PDGF-induced mesangial cell proliferation and extracellular matrix expression. PCNA, Fn and TGF-ßl expressions were attenuated significantly. Conclusions PDGF can enhance periostin protein expression and increase mouse mesangial cell proliferation and extracellular matrix accumulation. Periostin shRNA vector can partially reverse PDGF-induced mesangial cell proliferation and extracellular matrix generation.

Progress relationship between periostin and periodontitis / 华西口腔医学杂志

Periostin, a kind of matricellular protein highly expressed in periodontal ligament and periosteum, is an important regulator of the integrity of periodontal ligament and periodontitis processes. Periostin has been shown to play a positive role in the recovery of periodontitis. This paper reviews relevant literature about the role of periostin in periodontal tissue and periodontitis.

Expression of periostin in small cell lung cancer and its effect on chemoresistance / 中国胸心血管外科临床杂志

@#Objective    To detect the difference of periostin expression in small cell lung cancer (SCLC) cell, and explore its effect on chemoresistance of SCLC patients. Methods    The expression of periostin in mRNA and protein was detected by RT-PCR and Western blot analysis in SCLC H69 and multidrug resistant strain H69AR. The expression of periostin was up-regulated by recombinant plasmid-periostin in H69 cell. The survival rate in the transfected group was different from that of the negative control group and uninterrupted group. Results    The expression of periostin mRNA and protein in the sensitive strain H69 was lower than that of the multidrug resistant strain H69AR (P<0.05). The recombinant periostin-plasmid was transfected into H69 cells and at the same concentration of chemotherapeutic drugs (cisplatin, etoposide) the survival rate increased significantly (P<0.05). The positive expression rate of periostin in SCLC tissues was 67.44%, and the sensitivity of the chemotherapy group was lower than that of the drug resistant group (P<0.05). Conclusion    The expression of periostin in SCLC cell H69 is significantly lower than that of the multidrug resistant strain H69AR and overexpression of periostin increases resistance of the sensitive strain H69 and hence periostin may be involved in SCLC chemoresistance.

Serum Periostin Levels: A Potential Serologic Marker for Toluene Diisocyanate-Induced Occupational Asthma

PURPOSE: Toluene diisocyanate (TDI) is a leading cause of occupational asthma (OA). Periostin is a matricellular protein implicated in type 2 immunity-driven asthma. Its pathogenic role in TDI-OA has not been completely elucidated. The present study was performed to investigate the role of periostin in TDI-OA. MATERIALS AND METHODS: Serum periostin levels were measured in subjects with TDI-OA, asymptomatic TDI-exposure controls (AECs), non-occupational asthmatics (NAs), and unexposed normal controls (NCs). To understand the mechanism by which TDI induces periostin production, primary small airway epithelial cells (SAECs) were cultured under stimulation of TDI and neutrophils from asthmatic patients. RESULTS: Fifty-three subjects with TDI-OA, 71 AECs, 67 NAs, and 83 NCs were enrolled. Serum periostin levels were significantly higher in TDI-OA subjects than in AECs (p=0.001), NAs (p < 0.001), and NCs (p < 0.001). In TDI-exposed subjects (TDI-OA and AEC), the PC20 methacholine levels were significantly lower in subjects with a higher periostin level than in those with a lower periostin level. TDI exposure did not increase periostin production directly by SAECs; however, periostin production increased significantly after co-culture with TDI and neutrophils, which was suppressed by an antioxidant. In addition, increased release of TGF-β1 was noted from SAECs when exposed to TDI and neutrophils, which was also suppressed by an antioxidant. CONCLUSION: These results suggest that an increased periostin level may contribute to the progression of airway inflammation to remodeling in TDI-exposed workers. A high serum periostin level is a potential serologic marker of the phenotype of TDI-OA.

Serum Periostin Is Negatively Correlated With Exposure to Formaldehyde and Volatile Organic Compounds in Children

Epidemiological studies have shown that exposure to tobacco smoke causing irritation and inflammation in the airways tends to reduce serum periostin concentrations in adults. We now investigate prospective cross-sectional study on 135 Korean students aged 7 years in the first grade who were participating in the Seongnam Atopy Project for Children's Happiness 2016 (SAP2016) cohort. To the best of our knowledge, this is the first study to show significant inverse correlations between serum periostin concentration and exposure to xylene and formaldehyde in children. Our findings suggested the need for caution in using the serum periostin level as a marker for allergic diseases, since exposure to volatile organic compounds and formaldehyde may confound the interpretation of these results.

Study on the association between the expression of periostin protein and the occurrence and progression of knee osteoarthritis / 中华风湿病学杂志

Objective To study the association between the expression of periostin and the occurrence and progression of knee osteoarthritis (OA) in synovial fluid.Methods The expression level of periostin in the synovial fluid of healthy people and patients with different stages of OA was tested.Furthermore,60 surgical-induced OA rat model were divided into two groups,the sham operation group had only implemented slit suture,and the OA model group had one side anterior cruciate ligament transected.The expression of periostin in intra-articular injection samples were analyzed at 1,2,4,8,12 week.Fluorescence molecular tomography (FMT) were performed after surgery at 4,8,12 week on the surgery knee.Gross morphologic lesions on the tibial plateau in rats were visualized by India ink staining,toluidine blue staining,cartilage permeation test.The synovium were visualized by HE staining and periostin were detected by immunohistoc hemistry.The measurement data were compared by one factor analysis of variance test.Results The expression of periostin in cartilage was lower in late-stage OA than the one from normal and early-stage OA (F=13.95,P＜0.01).The FMT showed that there was no obvious change in the extent of chronic inflammation in the sham operation group,and the chronic inflammatory degree of the OA model group gradually increased as time went on.Toluidine blue staining and cartilage permeation test showed that the cartilage degeneration in rat model of OA became more and more serious with time.There was no stastically significant difference of the periostin in control groutp at different time stage (F=0.67,P=0.53).The periostin in the intra-articular increased at first and then decreased with the development of OA (F=11.0,P＜0.05).HE staining of synovial tissue showed that the degree of synovial hyperplasia was consistent with the degree of degeneration of joints.With the extension of time,the expression of periostin in synovial tissue increased gradually.Conclusion The expression of periostin in human synovial fluid is low in normal knee joint,increases in early and middle stages,and decreases in late stage.The rat model indicates that the expression of periostin increases first and then decreases with the development of OA,but the expression in synovium increases gradually with the development of OA.The increased expression of periostin in synovial fluid may serve as an early diagnostic marker for OA and downregulation of the periostin may be a start marker for the late OA.

Association of diabetic retinopathy with serum periostin and vascular endothelial growth factor / 眼科新进展

Objective To explore the changes in the serum periostin (PN) and vascular endothelial growth factor (VEGF) level in patients with diabetic retinopathy (DR) and the clinical significance.Methods The serum samples from 53 patients with diabetes mellitus (DM) as case group and 50 healthy subjects as control group were collected and compared in this study.And the DM patients included 15 patients with DM without fundus lesions (DM group),18 patients with non-proliferative diabetic retinopathy (NPDR,NPDR group) and 20 patients with proliferative diabetic retinopathy (PDR,PDR group).The serum levels of PN and VEGF were analyzed by ELISA assay,and the correlation of DR with serum PN and VEGF levels was evaluated.Results The differences in serum PN and VEGF between the case group and control group were statistically significant (both P ＜ 0.05).And there were significant difference in PN and VEGF levels among the DM group,NPDR group,PDR group and control group (all P ＜ 0.05).Meanwhile,there was no significant difference in serum PN between the DM group and NPDR group (P ＞ 0.05),but there were statistically significant differences among the other groups (all P ＜ 0.05).There were statistically significant differences in serum VEGF among the four groups (all P ＜ 0.05).And finally,positive correlations were found between PN and VEGF in the NPDR group and PDR group (r =0.483,0.509,both P ＜ 0.05).Conclusion PN and VEGF play an active role in the initiation and development of DR,and they have a close correlation with the neovascularization and fibrovascular membrane of the advanced stage of DR.

Expression differences and significance of periostin in eyelid basal cell carcinoma associated fibroblasts and-normal fibroblasts / 眼科新进展

Objective To investigate the expression differences and significance of periostin (PN) in eyelid basal cell carcinoma associated fibroblasts (BCAFs) andnormal fibroblasts (NFs) after separation,culture,purification and identification.Methods The third generation of purified BCAFs and NFs was selected,and the concentrations of cell suspensions were modulated to 20 × 106 L-1 by trypsin,and then the cell suspension were seeded and cultured in 6-well plate by 2 mL per well.The cell culture supernatants were collected when BCAFs and NFs were cultured by serum-free medium for 48 h,then the content of PN in cell culture supernatants from BCAFs and NFs was detected by enzyme-linked immunosorbent assay (ELISA).The glass coverslips were placed at the bottom of the 6-well plate to make cell slides,and then the expression of PN in BCAFs and NFs cells were tested by immunofluorescence staining.Results ELISA showed that the content of PN in cell culture supernatants from BCAFs and NFs was (9.26 ± 2.35) μg · L-1 and (2.57 ± 0.41) μg · L-1.And the expression level of PN in BCAFs tested by immunofluorescence staining technology was higher than that in NFs cells,and the differences were statistically significant (all P ＜ 0.05).Conclusion The expression and secretion of PN in the eyelid BCAFs were highly enhanced when compared with NFs,suggesting that periostein may promote or inhibit the occurrence and development of the eyelid basal cell carcinoma in the microenvironment of the eyelid basal cell carcinoma.