Osteoporosis is a disease marked by reduced bone mass, leading to an increased risk of fractures or broken bones. Bone formation is mediated by recruiting mesenchymal stem cells (MSCs). Elucidation of the molecular mechanisms that regulate MSC differentiation into osteoblasts is of great importance for the development of anabolic therapies for osteoporosis and other bone metabolism-related diseases. microRNAs (miRNAs) have been reported to have crucial roles in bone development, osteogenic differentiation and osteoporosis pathophysiology. However, to date, only a few miRNAs have been reported to enhance osteogenesis and regulate the suppressive effect of glucocorticoids on osteogenic differentiation. In this study, we discovered that miR-216a, a pancreatic-specific miRNA, was significantly upregulated during osteogenic differentiation in human adiposederived MSCs (hAMSCs). The expression of miR-216a was positively correlated with the expression of bone formation marker genes in clinical osteoporosis samples. Functional analysis demonstrated that miR-216a can markedly promote osteogenic differentiation of hAMSCs, rescue the suppressive effect of dexamethasone (DEX) on osteogenic differentiation in vitro and enhance bone formation in vivo. c-Cbl, a gene that encodes a RING finger E3 ubiquitin ligase, was identified as a direct target of miR-216a. Downregulation of c-Cbl by short hairpin RNAs can mimic the promotion effects of miR-216a and significantly rescue the suppressive effects of DEX on osteogenesis. Pathway analysis indicated that miR-216a regulation of osteogenic differentiation occurs via the c-Cbl-mediated phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The recovery effects of miR-216a on the inhibition of osteogenesis by DEX were attenuated after blocking the PI3K pathway. Thus, our findings suggest that miR-216a may serve as a novel therapeutic agent for the prevention and treatment of osteoporosis and other bone metabolism-related diseases.
Malignant change of endometriosis in a cesarean scar (CS) is rare. We report a case of carcinosarcoma arising from atypical endometriosis in a CS scar, which was successfully treated with complete excision of the lesion and repair of the abdominal wall defect with autologous skin-muscle flap graft. A 41-year-old woman presented with a recurrent endometriosis in a CS scar. Within 16 years it changed from benign to atypical endometriosis and finally to carcinosarcoma after three operations. Complete excision of the tumor was performed, with a big defect of abdominal wall successfully repaired by autologous pedicle skin-muscle graft. The diagnosis of carcinosarcoma arising from atypical endometriosis was confirmed histologically. The lesion recurred 6 months after the fourth operation. She died of disease 15 months after the fourth operation. This case demonstrated that long-standing recurrent scar endometriosis could undergo malignant changes and should be made aware. The primary treatment is complete surgical excision.
With 1.3 billion people, China has the largest population in the world, and therefore has the largest population of persons with haemophilia (PWH). As there is no national registry for haemophilia, it is difficult to ascertain how many PWH have actually been diagnosed. Between January 1983 and June 2002, 1312 patients with coagulation disorders were referred to our hospital, and 1190 patients were evaluable. Among them, 1069 (89.8%) patients had haemophilia, 68 had vWD, 20 had factor XI deficiency, 10 had acquired factor VIII inhibitor and 23 had other coagulation disorders. Of the 1069 PWH, 14.7% were unclassified, 38.4% severe, 35.7% moderate and 11.1% mild. If the unclassified cases were excluded, 45.1% were severe, 41.9% moderate and 13.0% mild. Twenty-nine of the 68 vWD patients had vWF:Ag <5%, and subcategorized as type 3 vWD. Because vWF multimer analysis was not performed in our centre, the remaining vWD patients were not subdivided.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.