Role of BMP3 in progression of gastric carcinoma in Chinese people

AIM:To investigate the relation between gastric cancer and microsatellite instability(MSI),loss of heterozygosity(LOH)and promoter region methylation.METHODS:Fifty primary gastric carcinoma specimens were collected from patients with no family history of cancer.In addition,normal tissues were also collected from patients as controls.DNA was extracted by polymerase chain reaction for single-strand conformation polymorphism,bisulfite DNA sequencing,and methylation-specific band analysis.RESULTS:The positive rate for MSI and LOH in gastric carcinoma was 16%and 20%,respectively.According to the tumor,node and metastasis staging system,the LOH frequency was higher in gastric carcinoma at stages Ⅲ and Ⅳ than in gastric carcinoma at stagesⅠ and Ⅱ(P=0.01),which was also significantly correlated with lymph node metastasis and clinicopathological characteristics of gastric carcinoma.Methylation of bone morphogenetic protein 3(BMP3)gene promoter was detected in 64.44% of gastric carcinoma tissue samples.However,no statistical significance was observed between promoter region methylation and carcinoma differentiation.Interestingly,the BMP3 gene methylation rate was 71.05% and 28.58%,respectively,in MSI positive and negative cases(P=0.031),suggesting that BMP3 genetic instability and promoter methylation are initiated during gastric carcinogenesis.LOH was detected mostly in the late stages of gastric carcinoma,indicating that gastric carcinoma at late stages has a higher infiltration and a poorer prognosis.CONCLUSION:Promotor region methylation of the BMP3 gene may cause gastric carcinoma in Chinese people.

Wnt3a enhances bone morphogenetic protein 9-induced osteogenic differentiation of C3H10T1/2 cells

Background Bone morphogenetic protein 9 （BMP9） and Wnt/13-catenin signaling pathways are able to induce osteogenic differentiation of mesenchymal stem cells （MSCs）, but the role of Wnt/13-catenin signaling pathway in BMP9-induced osteogenic differentiation is not well understood. Thus, our experiment was undertaken to investigate the interaction between BMP9 and Wnt/13-catenin pathway in inducing osteogenic differentiation of MSCs. Methods C3H10T1/2 cells were infected with recombinant adenovirus expressing BMP9, Wnt3a, and BMPg＋Wnt3a. ALP, the early osteogenic marker, was detected by quantitative and staining assay. Later osteogenic marker, mineral calcium deposition, was determined by Alizarin Red S staining. The expression of osteopotin （OPN）, osteocalcin （OC）, and Runx2 was analyzed by Real time PCR and Western blotting. In vivo animal experiment was carried out to further confirm the role of Wnt3a in ectopic bone formation induced by BMP9. Results The results showed that Wnt3a enhanced the ALP activity induced by BMP9 and increased the expressions of OC and OPN, with increase of mineral calcium deposition in vitro and ectopic bone formation in vivo. Furthermore, we also found that Wnt3a increased the level of Runx2, an important nuclear transcription factor of BMP9. Conclusion Canonical Wnt/13-catenin signal pathway may play an important role in BMP9-induced osteogenic differentiation of MSCs, and Runx2 may be a linkage between the two signal pathways.