Background:The A2BAR signals via cAMP. Cyclic AMP signaling has been shown to regulate MSC differentiation. Results: A2BAR KO mice have reduced differentiation of osteoblasts, a mild osteopenic phenotype, and impaired fracture physiology. A2BAR activation increases the differentiation of osteoblasts. Conclusion: The A2BAR regulates bone homeostasis. Significance: A2BAR signaling is a component of bone homeostasis, particularly after injury.

Mast cell activation through the high affinity IgE receptor FcεRI leads to the release of mediators involved in immediate-type allergic reactions. While antibodies against the tetraspanins CD63 and CD81 inhibit FcεRI-induced mast cell degranulation, the intrinsic role of these molecules in FcεRI-induced mast cell activation is unknown. In mast cells, CD63 is expressed at the cell surface and in lysosomes (particularly secretory lysosomes that contain allergic mediators). Here, we investigated the role of CD63 in mast cells using a CD63 knockout mouse model. CD63-deficiency did not affect in vivo mast cell numbers and tissue distribution. Bone-marrow-derived mast cells (BMMC) developed normally in the absence of CD63 protein. However, CD63-deficient BMMC showed a significant decrease in FcεRI-mediated degranulation, but not PMA/ionomycin-induced degranulation, as shown by β-hexosaminidase release assays. The secretion of TNF-α, which is both released from granules and synthesized de novo upon mast cell activation, was also decreased. IL-6 secretion, and production of the lipid mediator leukotriene C4 were unaffected. There were no ultrastructural differences in granule content and morphology, late endosomal/lysosomal marker expression, FcεRI-induced global tyrosine phosphorylation, and Akt phosphorylation. Finally, local reconstitution in genetically mast cell-deficient Kitw/w-v mice was unaffected by the absence of CD63. However, the sites reconstituted with CD63-deficient mast cells developed significantly attenuated cutaneous anaphylactic reactions. These findings demonstrate that the absence of CD63 results in a significant decrease of mast cell degranulation, which translates into a reduction of acute allergic reactions in vivo, thus identifying CD63 as an important component of allergic inflammation.

In this so far largest correlation study between coronary angiography and high efficiency CZT SPECT imaging, a high sensitivity and accuracy for detecting obstructive epicardial CAD was found for this new SPECT camera technology.

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