Mesenchymal stem cells (MSCs) isolated from spinal ligaments with ectopic ossification have a propensity toward the osteogenic lineage. To explore epigenetic control of the osteogenic features of MSCs, we treated MSCs obtained from the spinal ligaments of ossification of yellow ligament (OYL) patients and non-OYL patients with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5AdC). We compared the non-OYL groups (untreated and treated with 5AdC) with the OYL groups (untreated and treated with 5AdC) by genome-wide microarray analysis. Next, we used methylated DNA immunoprecipitation combined with quantitative real-time PCR to assess gene methylation. Ninety-eight genes showed expression significantly increased by 5AdC treatment in MSCs from non-OYL patients but not from OYL patients. In contrast, only two genes, GDNF and WNT5A, showed significantly higher expression in OYL MSCs compared with non-OYL MSCs without 5AdC treatment. Both genes were hypermethylated in non-OYL MSCs but not in OYL MSCs. Small interfering RNA targeted to each gene decreased expression of the target gene and also several osteogenic genes. Both small interfering RNAs also suppressed the activity of alkaline phosphatase, a typical marker of osteogenesis. These results suggest that the osteogenic features of MSCs from OYL patients are promoted by unmethylated WNT5A and GDNF genes.

A 32‐year‐old woman was referred to our hospital because of severe psychosis and was found to have an ectopic ACTH‐producing thymic neuroendocrine tumor. Laboratory data revealed an elevated serum cortisol and plasma ACTH level, hypokalemia, and metabolic alkalosis. Chest computed tomography (CT) revealed an anterior mediastinal mass and multiple pulmonary nodules. As the patient was unable to communicate because of her consciousness disturbance, she was managed with artificial ventilation and deep sedation. Metyrapone and potassium supplementation were administered, and steroid psychosis gradually improved. Thoracic surgery was performed and the histopathological diagnosis was thymic neuroendocrine tumor with positive anti‐ACTH immunohistochemical staining. Here we present details of the case and review the literature.

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Background: The leading pathology of biliary atresia (BA) is in ammatory and brous obstruction of extrahepatic bile duct, butthe pathogenesis remains unclear.IL13 is a cytokine associated with allergies and in ammatory brosis, and periostin induces brogenesis by stimulation with IL13. We analyzed the involvement of IL13 and periostin in in ammatory brosis in the extrahepatic bile duct of BA patients.Materials and Methods: Surgically resected tissues from the hepatic hilar area of BA patients were immunostained with CD45, α-SMA, IL13 and periostin and statistically analyzed. Fibroblasts from the resected tissue were cultured with recombinant IL13, and periostin production was analyzed by quantitative polymerase chain reaction and Western blotting.Results: IL13 was stained in 93% of large and micro bile ducts, and 92.1% matched with the CD45 location (p=0.006) around the large bile ducts. Periostin staining correlated with the localization of IL13 and αSMA (p<0.001) around the large bile ducts. Periostin mRNA and protein were up regulated by IL13 stimulation in cultured broblasts.Conclusion: IL13 was associated with induced periostin expression by broblasts, playing a vital role in the pathogenesis of brogenesis around the extrahepatic bile duct in BA.

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