Search

Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to the end of pregnancy, may exert some anabolic effects, either directly or through the regulation of the IGF1 production. Other key regulators of bone metabolism, such as estrogens or prolactin, are elevated during pregnancy, but their role is uncertain. An increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) to osteoprotegerin (OPG) acts as an additional pro-resorbing factor in bone. The increase in bone resorption may lead to osteoporosis and fragility fracture, which have been diagnosed, although rarely. However, the condition is transitory as long-term studies do not link the number of pregnancies with osteoporosis. Prevention is limited by the lack of identifiable risk factors. When fractures are diagnosed, rest, analgesics, or, when indicated, orthopedic intervention have demonstrated efficacy. Systemic treatment with anti-osteoporotic drugs is effective, but the potential harm to the fetus imposes caution in their use.

Fundamento: Los mecanismos que desencadenan la osteogénesis todavía no están aclarados. El objetivo de este estudio fue valorar el papel de estroncio y calcio, aportados en distinto soporte molecular, como inductores de distintos mecanismos de estímulo osteoblástico, incluyendo proliferación, diferenciación y mineralización de células preosteoblásticas. Se investigó también la respuesta global genómica con la técnica de microarray. Métodos: Se diseñó un estudio experimental con células pre-osteoblásticas murinas MC3T3-E1, que fueron estimuladas durante 3 horas y 7 días. Se realizaron estudios bioquímicos y de expresión génica del genoma de ratón (Affymetrix). Resultados: El estroncio unido a ranelato (SrRn) fue el más potente inductor de la capacidad de mineralización, en comparación con los otros compuestos utilizados (2,55 veces respecto al control). Los estudios de expresión génica global mostraron que a las 3 horas cambian 2.030 genes de los cuales 1.644 genes son específicos de esta fase. Por el contrario, a 7 días de tratamiento sólo cambian 329 genes siendo específicos 147 genes. Los procesos biológicos más enriquecidos a las 3 horas fueron los involucrados en la regulación transcripcional (147 genes), procesos metabólicos (140 genes) y la fosforilación de proteínas (44 genes) entre otros, mientras que a 7 días hubo cambios relacionados con el ciclo celular (18 genes) y con el metabolismo de carbohidratos en general (12 genes). Conclusión: El estroncio unido al anión ranelato se comportó como el más potente inductor de la osteogénesis comparado con otros aniones como cloruro o hidróxidos. El estímulo a 3 horas presentó mayores cambios de expresión de genes en comparación a 7 días. Los procesos biológicos afectados pueden ser útiles para especular sobre cascadas de señalización involucradas en la activación osteoblástica y sobre nuevas dianas moleculares con fines terapéuticos. Background: The mechanisms which trigger osteogenesis are not yet clear. The objective of this study was to evaluate the role of strontium and calcium, provided in different molecular forms, as inductors of different mechanisms of osteoblast stimulus, including proliferation, differentiation and mineralisation of preosteoblast cells. The whole genomic response was also investigated using the microarray technique. Methods: An experimental study was designed with murine preosteoblast cells MC3T3-E1, which were stimulated for 3 hours and 7 days. Biochemical and genome gene expression studies of mouse (Affymetrix) were carried out. Results: Strontium bonded with ranelate (SrRn) was the most powerful inductor of the capacity of mineralisation in comparison with the other compounds used (2.55 times that of the control). The studies of whole gene expression showed that after 3 hours 2030 genes change, of which 1644 are specific to this phase. On the other hand, after 7 days of treatment only 329 genes change, of which 147 are specific. The biological processes most enriched after 3 hours are those involved in the regulation of transcription (147 genes), metabolic processes (140 genes) and protein phosphorylation (44 genes) among others, while at 7 days these are changes relating to the cell cycle (18 genes) and carbohydrate metabolism in general (12 genes). Conclusion: Strontium bonded with the ranelate anion performed as the most powerful inductor of osteogenesis compared with other anions such as chloride or the hydroxides. The stimulation for 3 hours showed greater changes in gene expression in comparison with 7 days. The biological processes affected may be useful in speculating on the signalling cascades involved in the activation of the osteoblast, and on new molecular targets for therapeutic purposes.