Subject(s)
Anthrax , Biological Warfare Agents , Bioterrorism , Ethics, Research , Laboratory Personnel/ethics , Laboratory Personnel/legislation & jurisprudence , Scientific Misconduct , Social Responsibility , Biological Warfare Agents/ethics , Biological Warfare Agents/legislation & jurisprudence , Bioterrorism/ethics , Bioterrorism/legislation & jurisprudence , Character , Education, Professional/standards , Ethics, Research/education , Government Regulation , Humans , Organizational Culture , Scientific Misconduct/ethics , Scientific Misconduct/legislation & jurisprudence , United StatesABSTRACT
BACKGROUND: Annexin 1 is a 37-kDa protein that has complex intra- and extracellular effects. To discover whether the absence of this protein alters bone development, we monitored this event in the annexin-A1 null mice in comparison with littermate wild-type controls. METHODS: Radiographic and densitometry methods were used for the assessment of bone in annexin-A1 null mice at a gross level. We used whole-skeleton staining, histological analysis, and Western blotting techniques to monitor changes at the tissue and cellular levels. RESULTS: There were no gross differences in the appendicular skeleton between the genotypes, but an anomalous development of the skull was observed in the annexin-A1 null mice. This was characterized in the newborn annexin-A1 null animals by a delayed intramembranous ossification of the skull, incomplete fusion of the interfrontal suture and palatine bone, and the presence of an abnormal suture structure. The annexin-A1 gene was shown to be active in osteocytes during this phase and COX-2 was abundantly expressed in cartilage and bone taken from annexin-A1 null mice. CONCLUSIONS: Expression of the annexin-A1 gene is important for the normal development of the skull in mice, possibly through the regulation of osteoblast differentiation and a secondary effect on the expression of components of the cPLA2-COX-2 system.
Subject(s)
Annexin A1/genetics , Bone and Bones/abnormalities , Craniofacial Abnormalities/genetics , Gene Expression/physiology , Animals , Animals, Newborn , Bone Density , Bone Development/genetics , Craniofacial Abnormalities/metabolism , Craniofacial Abnormalities/pathology , Cyclooxygenase 2/metabolism , Female , Homozygote , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Osteogenesis , Phospholipases A/metabolismABSTRACT
This overview will focus on one aspect of neutrophil biology, which is the selective activation of the annexin 1 system in relation to the process of cell extravasation. Besides the current view about the biochemistry of annexin 1 and annexin 1 receptor(s) up-regulation within the microenvironment of the adherent neutrophils, we will also comment on the final result achieved by activation of the system, which is inhibition of neutrophil recruitment. In view of the historical link between annexin 1 and glucocorticoids, the potential for the annexin 1 system in mediating at least some of the anti-inflammatory actions of these powerful drugs is also discussed.
