The effects of OSM on proliferation and differentiation of osteosarcoma and nontransformed osteoblasts were analyzed. OSM downregulates osteoblast markers but induces the glial fibrillary acidic protein by the combined activation of PKCdelta and STAT3, offering new lines of therapeutic investigations. INTRODUCTION: Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family implicated in embryonic development, differentiation, inflammation, and regeneration of various tissues, mainly the liver, bone, and the central nervous and hematopoietic systems. One particularity of OSM relies on its growth inhibitory and pro-differentiating effects on a variety of tumor cell lines such as melanoma, providing arguments for a therapeutic application of OSM. The objective of this study was to analyze the effects of OSM on osteosarcoma cell lines proliferation and differentiation. MATERIALS AND METHODS: Proliferation was analyzed by 3H thymidine incorporation. Differentiation was analyzed by semiquantitative RT-PCR and immunocytochemistry for various markers. Alizarin red S staining was used to evaluate bone nodule formation. Morphological changes were studied by confocal and electron microscopy. Western blotting, kinases inhibitors, and dominant negative STAT3 were used to identified the signaling pathways implicated. RESULTS: OSM inhibits the growth of rat osteosarcoma cell lines as well as normal osteoblasts, in correlation with induction of the cyclin-dependent kinases inhibitor p21WAF1. However, OSM reduces osteoblast markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein, leading to strong inhibition of mineralized nodule formation. This inhibitory effect is restricted to mature osteoblasts and differentiated osteosarcoma because OSM effectively stimulates osteoblast markers and bone nodule formation in early, but not late, bone marrow mesenchymal stem cell (BMSC) cultures. In osteosarcoma cells or BMSC, OSM induces expression of the glial fibrillary acidic protein (GFAP) as well as morphological and ultrastructural changes, for example, elongated shape and bundles of microfilaments in cell processes. Rottlerin (PKCdelta inhibitor), and to a lesser degree UO126 (MEK/ERK inhibitor), prevents the loss of osteoblastic markers by OSM, whereas dominant negative STAT3 prevents GFAP induction. CONCLUSIONS: These results highlight the particular gene expression profile of OSM-treated osteosarcoma cells and BMSCs, suggesting either a osteocytic or a glial-like phenotype. Together with the implication of PKCdelta, ERK1/2, and STAT3, these results offer new lines of investigations for neural cell transplantation and osteosarcoma therapy. 相似文献
Changes in semen parameters are presented for 4708 patients treated for infertility. The largest group comprised patients
with oligoasthenozoospermia of various grades (57.7%). Improvement in the seminal state was noted in 70.3%. The percentage
of achieved normospermia increased proportionally to the initial semen state. Pregnancy rate also increased proportionally
to the initial seminal state.
Among the patients' wives 20.4% conceived: 28.2% of these pregnancies had occurred after having achieved normospermia, while
in 71.8% the seminal states were still below the accepted normal values. 相似文献
We describe a rare syndrome in a Finnish family, in which the father and his two sons are congenitally deaf and also exhibit corneal vascularization, and hyperkeratosis of the skin of the palms, soles, elbows and knees. In addition, all 3 suffer from fungal infections of the skin and nails. We also describe a fourth, sporadic case of a 9-year-old girl with the same disease. The KID (k = keratitis, i = ichthyosis, d = deafness) syndrome is an ectodermal dysplasia that probably arises through mutation, and is transmitted as an autosomal dominant in the family described by us. 相似文献
The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8).
Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person. 相似文献
As part of a world survey of the habits, knowledge and attitudes of medical students regarding tobacco we report a study in 15 medical schools from nine Asian countries. Some 1646 first year and 1587 final year students were included, of whom 59% were male. The prevalence of daily smoking in males was 4% in first year and 11% in final year; of occasional smoking 18% and 24% respectively, both with considerable variations between countries. The rates were very low in women. Male exsmokers varied from 3% to 24% in different centres. Overall, 33% of smokers had made a serious attempt to quit; 44% expected to have succeeded within 5 years. Over 80% of non- or exsmokers, but only 60% of smokers, thought smoking was harmful to health. There was gross underestimation of tobacco's causal role in a number of important diseases, e.g. coronary artery disease, peripheral vascular disease, emphysema, bladder cancer and neonatal mortality. There were notable defects both in training and in motivation to counsel smoking patients. There was only partial knowledge of legislative and other measures to discourage smoking, e.g. only 44% of final year students (26% of smokers) thought increased taxation an important measure. In knowledge and attitudes there was little difference between the sexes, but in most aspects smokers had notably lower scores. 相似文献