ABSTRACT
Inhibin-α, a member of the transforming growth factor (TGF-ß) superfamily, has been involved in bone turnover during the menopausal transition via endocrine effects, and it was previously reported that inhibins may antagonize the function of BMPs. Certainly, one of the most important functions of BMPs is to induce osteogenic differentiation. BMP9 as one of the most potent BMPs to induce osteogenic differentiation has gotten more and more attentions. Nonetheless, the effects of inhibin-α on osteogenesis remain unknown. Besides, mesenchymal stem cells (MSCs) with the ability to differentiate into multiple mesenchymal lineages, including osteoblasts, adipocyte, chondrocytes, and myoblasts in vitro, have become the promising seed cells for bone tissue engineering. Here, we investigated the role of inhibin-α on BMP9-induced osteogenic differentiation in MSCs and tried to discover the mechanism underlying this process. We found inhibin-α apparently reduced the classical osteogenic markers and the ectopic bone formation induced by BMP9. In addition, the ratio of OPG to RANKL is declined also in the presence of inhibin-α. For mechanism, we found that exogenous expression of inhibin-α inhibits BMP9-induced osteogenic differentiation through blocking BMP/Smad signal transduction and activating NF-κB signal which is repressed by BMP9. Thus, our findings indicated that inhibin-α has a negative effect on BMP9-induced osteogenic differentiation in MSCs, which may provide a novel insight into the regulation of skeletal development and new strategy for bone tissue engineering.
Subject(s)
Growth Differentiation Factors/genetics , Inhibins/genetics , Mesenchymal Stem Cells/metabolism , NF-kappa B/genetics , Osteogenesis/genetics , Smad6 Protein/genetics , Smad7 Protein/genetics , Animals , Bone and Bones/cytology , Bone and Bones/metabolism , Cell Differentiation , Cell Line , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Female , Gene Expression Regulation , Growth Differentiation Factor 2 , Growth Differentiation Factors/metabolism , HEK293 Cells , Humans , Inhibins/metabolism , Mesenchymal Stem Cells/cytology , Mice , Mice, Nude , NF-kappa B/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , RANK Ligand/genetics , RANK Ligand/metabolism , Rats , Signal Transduction , Smad6 Protein/metabolism , Smad7 Protein/metabolism , TransfectionABSTRACT
OBJECTIVE: To investigate the effects of Cyclin A1 on the proliferation of SKM-1 cells and its underlying role in myelodysplastic syndrome (MDS). METHODS: Cyclin A1 was knocked down with its small interfering RNA (siRNA). The efficiency of siRNA transfection was measured by Western blot and RT-PCR. Then the proliferation of SKM-1 cells and the expression of CDK2,RUNX1 and SRSF2 with and without knockdown of Cyclin A1 recorded and analysed respectively. RESULTS: Cyclin A1 was knocked down by siRNA after transfected for 48 h. The kncokdown of Cyclin A1 inhibited the proliferation of SKM-1 cells and down-regulated the expression of CDK2, RUNX1 and SRSF2, and these effects were at least partially mediated through RUNX1 and SRSF2 signaling pathway. CONCLUSION: Cyclin A1 plays an important role in the proliferation of SKM-1 cells. These findings provide new insights into the pathogenesis of MDS, and it may be a potential target in the treatment of MDS.
Subject(s)
Cell Proliferation , Cyclin A1/metabolism , Myelodysplastic Syndromes/metabolism , RNA, Small Interfering , Apoptosis , Cell Line, Tumor , Gene Knockdown Techniques , Humans , Myelodysplastic Syndromes/pathologyABSTRACT
OBJECTIVE: To report a case of rectal cancer in a patient with Peutz-Jeghers syndrome (PJS). CLINICAL PRESENTATION AND INTERVENTION: A 20-year-old woman with intermittent bloody stool of 4 months was admitted for examination. Gastroendoscopy revealed multiple polyps involving the stomach, small intestine, colon and a rectal adenocarcinoma. A diagnosis of PJS was made based on intestinal polyps with characteristic pathology and melanotic macules on the lips. After surgery and chemotherapy upon follow-up at 8 months, the patient did not have any signs of recurrence. CONCLUSION: This case showed that rectal carcinoma should be considered for young patients with PJS.
Subject(s)
Peutz-Jeghers Syndrome/epidemiology , Rectal Neoplasms/epidemiology , Adult , Diagnosis, Differential , Female , Humans , Peutz-Jeghers Syndrome/diagnosis , Peutz-Jeghers Syndrome/therapy , Rectal Neoplasms/therapyABSTRACT
BACKGROUND: Pseudomonas aeruginosa are normal flora in the human gastrointestinal (GI) tract, which on occasion cause GI tract infection. METHODS: We evaluated the clinical significance of a pure growth of P. aeruginosa in fecal specimens in previously healthy children. The records of 45 previously healthy children under 15 years of age who were seen between June 2000 and August 2006 and who had a pure growth of P. aeruginosa in the stool were retrospectively reviewed. RESULTS: Of the 45 children, 28 (62%) were infants, three of whom developed sepsis secondary to the pseudomonal infection; two of which died. Complications in another four included colonic perforation (in two), necrotizing enterocolitis (in one), and an anal ulcer resulting in anal stricture (in one). The seven children with complications were all infants. Although not all children in our study had complete data in laboratory determinations, the presence of bandemia, elevated C-reactive protein (CRP), anemia and hypoalbuminemia may be of clinical importance. CONCLUSION: P. aeruginosa growing in the stool of otherwise healthy children may indicate actual infection by the organism and may be associated with severe or even fatal disease, particularly in infants. Bandemia, elevated CRP, anemia, and hypoalbuminemia give further warning in these patients.
