Osteoblasts play key roles in the mechanisms of action of strontium ranelate.

BACKGROUND AND PURPOSE: Strontium ranelate reduces fracture risk in postmenopausal women with osteoporosis. Evidence from non-clinical studies and analyses of bone markers in phase III trials indicate that this is due to an increase in osteoblast formation and a decrease of osteoclastic resorption. The aim of this work was to investigate, in human cells, the mechanisms by which strontium ranelate is able to influence the activities of osteoblasts and osteoclasts. EXPERIMENTAL APPROACH: Human primary osteoblasts were used to examine effects of strontium ranelate on replication (thymidine incorporation), differentiation (Runx2 and alkaline phosphatase) and cell survival (cell counts and caspase activity). Osteoprotegerin (OPG) was measured by quantitative reverse transcription PCR (qRT-PCR) and elisa and receptor activator of NFkappaB ligand (RANKL) by qRT-PCR and Western blot. As strontium ranelate has been proposed as an agonist of the calcium-sensing receptor (CaSR), the involvement of CaSR in the effects of strontium ranelate on OPG and RANKL expression, and cell replication was examined using siRNA. KEY RESULTS: Strontium ranelate increased mRNA and protein levels of OPG and suppressed those of RANKL. Strontium ranelate also stimulated osteoblast replication and differentiation and increased cell survival under stress. Knocking down CaSR suppressed strontium ranelate-induced stimulation of OPG mRNA, reduction of RANKL mRNA, and increase in replication, indicating the involvement of CaSR in these responses. CONCLUSIONS AND IMPLICATIONS: Our results demonstrate that osteoblasts play a key role in the mechanism of action of the anti-fracture agent, strontium ranelate by mediating both its anabolic and anti-resorptive actions, at least in part, via activation of CaSR.

The influence of surface chemistry and topography on the contact guidance of MG63 osteoblast cells.

The purpose of the present study was to determine in vitro the effects of different surface topographies and chemistries of commercially pure titanium (cpTi) and diamond-like carbon (DLC) surfaces on osteoblast growth and attachment. Microgrooves (widths of 2, 4, 8 and 10 microm and a depth of 1.5-2 microm) were patterned onto silicon (Si) substrates using microlithography and reactive ion etching. The Si substrates were subsequently vapor coated with either cpTi or DLC coatings. All surfaces were characterized using atomic force microscopy (AFM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. Using the MG63 Osteoblast-Like cell line, we determined cell viability, adhesion, and morphology on different substrates over a 3 day culture period. The results showed cpTi surfaces to be significantly more hydrophilic than DLC for groove sizes larger than 2 microm. Cell contact guidance was observed for all grooved samples in comparison to the unpatterned controls. The cell viability tests indicated a significantly greater cell number for 8 and 10 microm grooves on cpTi surfaces compared to other groove sizes. The cell adhesion study showed that the smaller groove sizes, as well as the unpatterned control groups, displayed better cell adhesion to the substrate.

Lamellar body count as a predictor of neonatal lung maturity in high-risk pregnancies.

OBJECTIVES: To compare the usefulness of a lamellar body count, a fluorescence polarization assay, and the foam stability index for predicting neonatal lung maturity in high-risk pregnancies. SETTING: This study was conducted at the Department of Obstetrics and Gynecology and the Department of Pediatrics, Assiut University Hospital. DESIGN: A prospective clinical trail. SUBJECTS AND METHODS: This study was performed after recruiting 73 pregnant women, 52 with high-risk pregnancies (25 had diabetes and 27 had premature labor) and 21 with a healthy full-term singleton pregnancy as controls. All women were delivered in the Department of Obstetrics and Gynecology of Assiut University Hospital. The newborns with respiratory distress syndrome (RDS) were admitted in the neonatal intensive care unit of the Department of Pediatrics. Amniotic fluid specimens were obtained near delivery. Apgar score, vital signs, anthropometric data, and complete clinical examination results were available for all newborns, and particular emphasis was placed on signs of RDS. RESULTS: The incidence of RDS was 44.2% in the newborns of women who had experienced a high-risk pregnancy (of these, 82.6% were born preterm and 17.4% to diabetic mothers). We found that a lamellar body count is a good screening test for predicting neonatal lung maturity. It is as good as the fetal lung maturity assay by fluorescence polarization in some respects and better in others; moreover, it is better than the foam stability index test in all respects. A lamellar body count with cutoffs of 41 x 10(3)/microL and 18 x 10(3)/microL was a good predictor of low and high risks of RDS in newborns. Values between 19 x 10(3)/microL and 40 x 10(3)/microL were the best to predict an intermediate risk of RDS. CONCLUSION: Lamellar body count is a good screening test for predicting the degree of neonatal lung maturity.

Increase in synthesis of human monoclonal antibodies by transfected Sp2/0 myeloma mouse cell line under conditions of microgravity.

Microgravity can influence cell growth and function. A transfected Sp2/0 myeloma cell line P3A2 producing a human IgG1 anti-TNFa monoclonal antibody was cultivated in static culture, spinner flasks and simulated microgravity using a rotating wall vessel bioreactor. Microgravity significantly decreased cell growth (from 1.7 x 10(6) to 7.9 x 10(5) cells/ml), but facilitated the synthesis of antibodies, (1.8, 1.3 and 0.5 microg of anti-TNFalpha hmAb per 10(6) viable cells for cells cultivated under microgravity, in spinner flasks and static cultures, respectively). The results suggest that microgravity could be applied to improve the specific productivity of cell lines producing potentially important therapeutic proteins.

Isotopic and hydrogeochemical evaluation of groundwater at Qusier-Safaga area, eastern desert, Egypt.

The groundwater resources of the El-Qusier-Safaga area on the Red Sea coastal zone have still to be utilised fully for social and economic development. In the present study, an inventory of recharge sources and quality of groundwater in different water bearing formations is made to assist in management of these vital resources. From a hydrochemical point of view, the origin of salinity in the five investigated aquifers are mainly dissolution of terrestrial minerals, leaching of soilsvia floods or ion exchanges processes. Stable isotope data clarify the interaction between different aquifers and indicate that the source of recharge is mainly meteoric water originating from palaeowater of the Pleistocene pluvial period, and from local precipitation as well as some marine water. Evaluation of the groundwater quality for domestic, irrigation and industrial purposes is discussed.