Respuesta de preosteoblastos a compuestos de estroncio o calcio: proliferación, diferenciación, mineralización y respuesta génica global

Abstract

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.

The effect of Mg–Ca–Sr alloy degradation products on human mesenchymal stem cells

“…In addition to different alloy extracts, Sr‐only extracts were included, to determine potential differences between Sr‐only and Mg–Ca–Sr co‐administration. Two different concentrations of the Sr compound was selected for testing, one corresponding to expected Sr amounts eluded from the alloy, and one concentration in the order of magnitude shown in literature to affect bone cell expression . In the following sections, results are presented by Mg/Ca/Sr content (expressed in mM), as well as extract numbers, as denoted in Table , for ease of navigation.…”

“…Forward Reverse magnitude shown in literature to affect bone cell expression. 13,28 In the following sections, results are presented by Mg/Ca/Sr content (expressed in mM), as well as extract numbers, as denoted in Table II, for ease of navigation.…”

“…11 In hMSC cultures, in both the absence and presence of serum, addition of certain Mg concentrations can upregulate different gene expressions involved in tissue regeneration or osteogenic differentiation. 12 Multiple in vitro studies have also reported on the enhanced effects of Mg or Ca on osteoblast activity, such as improved growth [13][14][15] and alkaline phosphatase (ALP) expression. 14,15 Both oral administration and in vitro studies confirm Sr can pharmacologically increase bone formation and reduce bone resorption.…”

Bone Regeneration Induced by Strontium Folate Loaded Biohybrid Scaffolds

“…In this regard, experimental results showed that Sr administration increases the number of osteoblasts, decreases the number of osteoclasts, and promotes matrix formation. Notably, besides the effect on bone cells population and bone micro-architecture, Sr increases the mechanical resistance of bone through changes in the properties of bone matrix [14,46].…”

“…Successive waves of changes in gene expression pattern occurs within 0–7 days, which seems to be required to initiate the differentiation of pre-osteoblasts to a mineralizing phenotype. The expression of many genes related to regulation of transcription, metabolic processes and transport of molecules change in this first phase of the maturation process [46]. In this regard, phosphorylation-dephosphorylation of proteins was shown to be the main biochemical event in this initial short time span; phosphorylation-dephosphorylation of proteins is well known to be involved in the regulation of metabolic pathways as well as in other important cellular processes.…”