RESUMEN
BACKGROUND: The role of bone morphogenetic proteins (BMPs) in bone healing has been demonstrated in numerous in vivo animal models. BMP-2, -4 and -7 have also been shown to stimulate the differentiation of human and animal stem cells into osteoblasts in vitro. There are, however, contradictory reports of BMPs causing apoptosis and inhibition of proliferation of osteoblastic cells. Therefore, a more complete understanding of the effects of BMP-2, -4 and -7 on human osteoblasts is required. METHODS: Cells of the immortalised human fetal osteoblastic line hFOB 1.19 were exposed to recombinant human (rh) BMP-2, -4 and -7. In addition, primary human osteoblasts were exposed to rhBMP-7. Cell proliferation was measured using a colorimetric assay. Apoptotic cells were detected using the TUNEL assay. RESULTS: The hFOB cells exposed in a dose-dependent manner to rhBMP-2, -4 and -7 had significantly lower rates of proliferation than non-treated cells, (p<0.01 for rhBMP-2, -4 and -7). The proliferation results for rhBMP-7 were replicated using primary human osteoblasts. Additionally, rhBMP-2, -4 and -7 induced a significantly higher rate of apoptosis in the hFOB cells, with a temporal and dose-dependent pattern (p<0.05), irrespective of the presence of serum growth factors. CONCLUSIONS: Despite interest in the potential clinical application of BMPs to improve bone healing, further studies are necessary to determine their full biological function before they can be used confidently in humans.
Asunto(s)
Apoptosis/efectos de los fármacos , Proteína Morfogenética Ósea 2/farmacología , Proteína Morfogenética Ósea 4/farmacología , Proteína Morfogenética Ósea 7/farmacología , Proliferación Celular/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Proteína Morfogenética Ósea 2/administración & dosificación , Proteína Morfogenética Ósea 4/administración & dosificación , Proteína Morfogenética Ósea 7/administración & dosificación , Línea Celular Transformada , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Etiquetado Corte-Fin in Situ , Osteoblastos/citología , Osteoblastos/fisiología , Proteínas Recombinantes/farmacología , Factores de TiempoRESUMEN
Female cigarette smoking has been implicated as having a detrimental effect on in-vitro fertilization (IVF) outcomes mediated through: (i) a diminished ovarian reserve (DOR), and (ii) an elevated pregnancy loss. Research is sparse regarding the effect of male smoking. The objective of this retrospective cohort study was to investigate the effect of male and female smoking on: (i) the collective quality of embryos selected for uterine transfer, and (ii) the likelihood of achieving an ongoing pregnancy at 12 weeks. A total of 498 consecutive IVF treatment cycles were analysed. Female smokers were significantly younger (P < 0.05) and achieved a better modified cumulative embryo score (mCES) (P < 0.05) than female non-smokers. Female age correlated inversely with the number of oocytes collected (r = -0.42, P < 0.01) and the number of oocytes in turn was important in terms of predicting mCES. The decreasing number of oocytes aspirated with increasing age was of a significantly stronger magnitude for female smokers than for female non-smokers (P < 0.05). Multiple logistic regression was used to determine whether smoking affected the likelihood of achieving a 12-week pregnancy. The mCES, tubal infertility and male smoking were found to be significant. Male smoking interacted with male age (P = 0.0164), indicating for male smokers a decrease of 2.4% in the likelihood of achieving a 12-week pregnancy with every 1-year increase in age. This is the first study to show that male smoking has a deleterious effect on pregnancy outcome among IVF patients. Our study supports the increased risk of DOR but fails to support the elevated incidence of pregnancy loss among female smokers. A reduced pregnancy rate was associated with male smoking possibly through pre-zygotic genetic damage. The growing realization of a paternal component of reproductive impairment suggests that studying the male is necessary.