RESUMO
Dlx5 plays an important role in the embryonic development of mineralized tissues. We hypothesized that Dlx5 also functions in regulating post-natal bone formation in mice. To prove this hypothesis, we infected 5-day-old bone sialoprotein (BSP)/avian retroviral receptor gene (TVA) transgenic mice with replication-competent retroviral vectors expressing wild-type Dlx5 (RCAS-Dlx5WT) and mutated Dlx5 at arginine (R) 31 of its homeodomain (RCAS-Dlx5RH). Immunohistochemistry indicated that RCAS-Dlx5WT increased BSP and osteopontin (OPN) expression, whereas it decreased that of osteocalcin (OC). RCAS-Dlx5RH mediated opposite effects. Semi-quantitative RT-PCR confirmed these results. Ex vivo overexpression of RCAS-Dlx5WT in BSP/TVA calvarial cells promoted, whereas that of RCAS-Dlx5RH inhibited, mineralized nodule formation as compared with that in control cells. Our results suggest that Dlx5 promotes expression of early markers of osteogenic differentiation and increases mineralization post-natally.
Assuntos
Osso e Ossos/metabolismo , Proteínas de Homeodomínio/genética , Osteogênese/genética , Animais , Arginina/genética , Proteínas Aviárias/genética , Calcificação Fisiológica/genética , Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica/genética , Vetores Genéticos/genética , Sialoproteína de Ligação à Integrina , Camundongos , Camundongos Transgênicos , Mutação/genética , Osteocalcina/genética , Osteopontina/genética , Fenótipo , Receptores Virais/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sialoglicoproteínas/genéticaRESUMO
Bone sialoprotein (BSP) is a major non-collagenous protein in mineralized tissues. BSP is also implied to be involved in tumor metastasis through its unique structure. Using the human breast cancer cell line MDA-231, we established both brain-seeking and bone-seeking cell clones. The brain-seeking cells (MDA4-231BR) showed no bone metastasis in an animal model. In this experiment, MDA-231BR cells were transfected with BSP cDNA and inoculated into the hearts of nude mice. All five nude mice which received BSP-transfected MDA-231BR cells developed bone metastases, while no bone lesions were observed in the control group. Histological examination revealed invasion of tumor cells into the endosteal space and erosion of the bone margin. Some animals were crippled due to large lesions. These results suggest that BSP may impart to breast cancer cells the capacity to metastasize and thus play an important role in bone metastasis of malignant tumors.
Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Sialoglicoproteínas/fisiologia , Animais , Neoplasias Encefálicas/secundário , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , DNA Complementar/genética , Modelos Animais de Doenças , Coração , Humanos , Sialoproteína de Ligação à Integrina , Camundongos , Camundongos Nus , Transplante de Neoplasias , Sialoglicoproteínas/biossíntese , Sialoglicoproteínas/genética , TransfecçãoRESUMO
PIP: Due to the enormous success enjoyed by a short course in family planning directed to nurses, the faculty of the Saint-Jerome College, Canada, has developed and restructured it into a much longer and much more informative course, totalling 45 hours of instruction. Beside offering complete information in the scientific fundamentals of human reproduction, of reversible and irreversible contraceptive methods, and on induced abortion, the course discusses the physiological limits of contraception, and the psychological value of sexuality, fertility, and maternity.^ieng
