Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects the large part of SCD patients and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL) and osteoclast recruitment (Rank) with up-regulation of Il6 as pro-resorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). In order to interfer with the development of SBD, zoledronic-acid, a potent inhibitor of osteoclast activity/osteoclastogenesis and promoter of osteogenic lineage, was used in H/R exposed mice. Zoledronic-acid markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc) and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared to either normoxic or single H/R episode SCD mice. Zoledronic-acid used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment and increased osteoclast activity resulted from local hypoxia, oxidative stress and the release of pro-resorptive cytokine such as IL6. Zoledronic acid might act on both osteoclast and osteoblast compartment as multimodal therapy to prevent SBD

ASTRI Mini-Array Data Model Document

This document provides an overview of the data products of the ASTRI MA System, and their conceptual (and logical) data models. The goals are: - list the data products produced by the MA system and the related data product categories; - show the relationship between the data products; - define a short identifier for the data product; - refer to data streams in architectural diagrams without ambiguity; - define interfaces and data models

ASTRI Mini-Array Top Level Software Architecture

This document provides a comprehensive architectural overview of the ASTRI Mini-Array Software system (a.k.a MA Software or MA Software System), which manages observing projects, observation handling, array control and monitoring, data acquisition, archiving, processing and simulations of the Cherenkov and Intensity Interferometry observations, including science tools for the scientific exploitation of the ASTRI MA data. This document, using a number of different views, depicts different aspects of the Mini-Array software and describes the significant architectural decisions

ASTRI Mini-Array Top Level Use Cases Document

To capture the greatest possible number of points of view during the requirements-gathering phase, the observation-related use cases have been developed and presented in this document. The goal is to understand how to serve the users of the ASTRI Mini-Array System. The Observation-related use cases describe how to perform observations from the proposal to the scientific exploitation of the observation from a user’s point of view and the commonalities of all the science-related use cases. This category includes calibration and other technical-related use cases. his document defines the Top Level Use Cases of the ASTRI MA project. The use cases contained in this document are part of the functional requirements of the MA Software System to describe the workflow. These requirements complement the functional and quality requirements provided in the "ASTRI Mini-Array Top Level Software Architecture" document

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