Mathematical model of physicochemical regulation of precipitation of bone hydroxyapatite

IntroductionFormation of hydroxyapatite in bone, dentin, and enamel occurs at restricted molecular sites of specific extracellular matrix proteins and is controlled by multiple mineralization inhibitors. However, the role of physicochemical factors, such as the availability of required ions and the saturation status of the aqueous environment in biological mineralization, is not fully understood. The goal of this study was to use mathematical modeling to describe the complex physicochemical environment permissive to the precipitation of biological hydroxyapatite.MethodsWe simulated the processes occurring in the bone interstitial fluid (ISF) defined as an aqueous environment containing seven chemical components (calcium, phosphate, carbonate, sodium, potassium, magnesium, and chloride) that form 30 chemical species. We simulated reversible equilibrium reactions among these chemical species, and calculated supersaturation for hydroxyapatite and its precipitation rate using kinetic theory.Results and DiscussionThe simulated ISF was of correct ionic strength and predicted the equilibrium component concentrations that were consistent with the experimental findings. Supersaturation of physiological ISF was ~15, which is consistent with prior findings that mineralization inhibitors are required to prevent spontaneous mineral precipitation. Only total calcium, total phosphate and to a lesser degree total carbonate affected ion availability, solution supersaturation and hydroxyapatite precipitation rate. Both calcium and phosphate levels directly affected hydroxyapatite precipitation, and phosphate was affected by pH, which additionally influenced hydroxyapatite precipitation. Integrating mathematical models capturing the physiochemical and biological factors regulating bone mineralization will allow in silico studies of complex clinical scenarios associated with alterations in ISF ion composition, such as rickets, hypophosphatemia, and chronic kidney disease

Modernization of the approach to usage of region’s budget resources in the conditions of information economy development

The purpose of the article is to substantiate the necessity and to develop recommendations for modernizing the approach for usage of region’s budget resources in the conditions of the information economy creation. The methodological provision of verification of the offered hypothesis includes the specially developed method for evaluating the effectiveness of usage of region’s budget resources from the position of the information economy creation. For calculations, the article uses the information and analytical materials of the Russian specialized institutions that study the processes of development of the information economy: “Research Financial Institute”, Ministry of Communications and Mass Communications of the Russian Federation, and expert and ranking organizations – the State Management and CNews. It is proved that the traditional approach to usage of region’s budget resources, which is applied in modern Russia, contradicts the general national course for development of the information economy, as it does not stimulate the formation of information society and development of information and technological spheres of the regional economy and does not allow for development of interaction and cooperation of all interests parties within the budget process, which confirms the offered hypothesis. To solve the determined problem, the authors develop the modern approach to the usage of region’s budget resources in the conditions of the information economy creation and offer practical recommendations for modernizing the existing approach in modern Russia.peer-reviewe

Influence des flux de calcium sur la contrainte de cisaillement agissant sur les ostéocytes dans l'os cortical

Nous avons modélisé l'écoulement du fluide encerclant les cellules osseuses mécano-sensibles (ostéocytes). Le but de cette étude est d'améliorer nos modèles précédents en incluant des flux de calcium apparaissant lors de la dissolution ou de la précipitation de la matrice osseuse. Même si ces flux ne semblent pas altérer de manière significative la vitesse du fluide, ils peuvent changer le cisaillement ressenti par les ostéocytes. Par conséquent, nous avons examiné la façon dont de tels échanges chimiques affectent l'écoulement du fluide et donc la mécano-sensibilité des ostéocytes

Exosomal release of L-plastin by breast cancer cells facilitates metastatic bone osteolysis

Bone metastasis from breast and prostate carcinomas is facilitated by activation of bone-resorbing osteoclasts. Using proteomics approaches, we have identified peroxiredoxin-4 (PRDX4) as a cancer-secreted mediator of osteoclastogenesis. We now report characterization of L-plastin in the conditioned media (CM) of MDA-MB-231 human breast cancer cells using immunoblotting and mass spectrometry. The osteoclastogenic potential of MDAMB-231 CM with siRNA-silenced L-plastin was significantly reduced. L-plastin was detected in cancer-derived exosomes, and inhibition of exosomal release significantly decreased the osteoclastogenic capacity of MDA-MB-231 CM. When added to osteoclast precursors primed with RANKL for 2 days, recombinant L-plastin induced calcium/NFATc1-mediated osteoclastogenesis to the levels similar to continuous treatment with RANKL. Using shRNA, we generated MDA-MB-231 cells lacking L-plastin, PRDX4, or both and injected these cell populations intratibially in CD-1 immunodeficient mice. Micro-CT and histomorphometric analysis demonstrated a complete loss of osteolysis when MDA-MB-231 cells lacking both L-plastin and PRDX4 were injected. A meta-analysis established an increase in L-plastin and PRDX4 mRNA expression in numerous human cancers, including breast and prostate carcinomas. This study demonstrates that secreted L-plastin and PRDX4 mediate osteoclast activation by human breast cancer cells

Intrauterine bone fractures in fetuses with osteogenesis imperfecta: a literature review and a case report

The article presents a literature review on intrauterine bone fractures in fetuses suffering from osteogenesis imperfecta. Prenatal ultrasound investigation of the condition is made to identify pathologically changed bone tissue including shortened and deformed limb segments and ribs, bone fractures and callus formation and widened intracranial sutures. Comprehensive clinical, paraclinical and radiological evaluations are produced after the birth to determine treatment strategy. Skeletal fractures in newborns are treated conservatively. With diagnosis of osteogenesis imperfect established medical treatment with bisphosphonates is administered to inhibit osteoclast-mediated bone resorption, facilitate bone mineralization and lower fracture incidence. The case report describes fractures of both femurs and left tibia in a female newborn suffering from osteogenesis imperfecta type III diagnosed in utero with ultrasonographic screening. The case presented highlights infant’s trauma-focused status, radiological findings and the treatment performed

Durand et al 2012 Supplemental figures

Objective. Our objective was to compare the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) from patients with osteoarthritis (OA) to that of PBMCs from self-reported normal individuals. Methods. PBMCs from 140 patients with OA and 45 healthy donors were assayed for CD14+ expression and induced to differentiate into osteoclasts (OCs) over 3 weeks in vitro. We assessed the number of the OCs, their resorptive activity, OC apoptosis, and expression of the following cytokine receptors: receptor activator of nuclear factor κB (RANK), interleukin-1 receptor type I (IL-1R1) and IL-1R2. A ridge logistic regression classifier was developed to discriminate OA patients from controls. Results. PBMCs from OA patients gave rise to more OCs that resorbed more bone surface than did PBMCs from controls. The number of CD14+ precursors was comparable in both groups, but there was less apoptosis in OCs obtained from OA patients. Although no correlation was found between osteoclastogenic capacity and clinical or radiologic scores, levels of IL-1R1 were significantly lower in cultures from patients with OA compared to controls. OC apoptosis and expression levels of IL-1R1 and IL-1R2 were used to build a multivariate predictive model for OA. Conclusion. During 3 weeks of culture under identical conditions, monocytes from patients with OA display enhanced capacity to generate OCs compared to cells from controls. Enhanced osteoclastogenesis is accompanied by increased resorptive activity, reduced OC apoptosis and diminished IL-1R1 expression. These findings support the possibility that generalized changes in bone metabolism affecting OCs participate in the pathophysiology of OA