Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone morphogenetic protein-6 (BMP-6) is a potent inducer of osteogenic differentiation and its expression is stimulated by 17beta-estradiol. The existence of a regulatory loop between sex steroids and BMP-6 is therefore reasonable to hypothesize. Here we determined whether the sex steroids 17beta-estradiol and dihydrotestosterone, and the phytoestrogen resveratrol can modulate BMP-6-induced alkaline phosphatase activity and osteocalcin expression. Mesenchymal cells of murine (osteoblastic MC3T3-E1 cells, preadipogenic ST2 cells, prechondrogenic ATDC5 cell) and human origin (osteosarcoma SaOS and HOS cells, primary bone marrow stromal cells) were cultured in the presence of recombinant BMP-6 under serum-free conditions. BMP-6 dose-, and time-dependently increased alkaline phosphatase activity in murine cell lines, but not in human cells. Osteocalcin expression was also increased upon stimulation with BMP-6. The presence of 17beta-estradiol, dihydrotestosterone, and resveratrol had no effect on BMP-6-induced alkaline phosphatase activity and osteocalcin expression. These data suggest that osteogenic differentiation in response to BMP-6 occurs independent of steroid hormones and resveratrol in mesenchymal cells that express basal receptor levels.
Cytokine
PMID:BMP-6-induced osteogenic differentiation of mesenchymal cell lines is not modulated by sex steroids and resveratrol. 1296 49

Eradicative levels of antitumor activity by cytokines and leukocytes have not yet been reached experimentally and are needed clinically. Only a limited number of human cancers respond to therapy with interferon (IFN), other cytokines, or mononuclear leukocytes despite significant antitumor activity in vitro. We studied the IFN and monocytic cell conditions that would lead to an eradicative effect using human cells in vitro. Targets of the IFN-activated monocytic cells were either four human tumor cell lines (human osteosarcoma [HOS], LOX melanoma, A549 lung tumor, and SNB-19 glioblastoma) or two diploid cell lines (WI38 and MRC5). An average of 30-90 colony-forming tumor target cells were cultured overnight in 96-well tissue culture plates prior to treatment with serially diluted IFN with or without activated elutriation-purified monocytes or lymphocytes. The target cell colonies were treated for 3 days. The colonies were then stained with crystal violet to determine the levels of antitumor activity. IFN-activated human monocytes reached an eradicative level (95%-100%) against three of four tumor cell lines. The eradicative level (1) was induced best in human monocytes activated by combined type I and II IFNs, (2) was effective against tumor cells that were growing for 24 h, (3) was specific for human tumors, as diploid human cells were not inhibited, and (4) required contact between the macrophage and the tumor cells. Also, for the first time, the minimal effective concentration (MEC) of IFNs to activate monocytes can approach those needed for antiviral activity. To our knowledge, this is the first report of near total eradication of many tumor cells, but not diploid cells, by IFN-activated monocytes. Because of its potency and specificity, the IFN-activated monocyte arm of the innate immune system may be a candidate for therapy of established tumors.
J Interferon Cytokine Res 2007 Feb
PMID:Clinical model: interferons activate human monocytes to an eradicative tumor cell level in vitro. 1731 43