beta2-adrenergic receptor signaling in osteoblasts contributes to the ...
beta2-adrenergic receptor signaling in osteoblasts contributes to the ...
beta2-adrenergic receptor signaling in osteoblasts contributes to the ...
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β2-ADRENERGIC RECEPTOR SIGNALINGIN OSTEOBLASTS CONTRIBUTES TO THE CATABOLICEFFECT OF GLUCOCORTICOIDS ON BONE• The skele<strong>to</strong>n is <strong>in</strong>nervated by sympa<strong>the</strong>tic nerves• Dur<strong>in</strong>g normal bone remodel<strong>in</strong>g, norep<strong>in</strong>ephr<strong>in</strong>e release <strong>in</strong> bones bysympa<strong>the</strong>tic neurons <strong>to</strong>nically suppresses bone formation and promotes boneformationSNSβ2ARNEOsteoblastBone formationBone resorptionLept<strong>in</strong>Bone mass• The relevance of β 2 AR <strong>signal<strong>in</strong>g</strong> <strong>to</strong> bone pathologies is unclear• Glucocorticoids, similarly <strong>to</strong> β 2 AR activation, cause bone loss by promot<strong>in</strong>gbone resorption and by <strong>in</strong>hibit<strong>in</strong>g bone formation
Dexamethasone promotes <strong>the</strong> responsivenessof differentiated <strong>osteoblasts</strong> <strong>to</strong> <strong>adrenergic</strong>stimulationAdrβ 2 /18Sexpression(foldInduction)8642d0 d2 d4 d8***604020cAMPAccumulation(fold <strong>in</strong>duction)****PretreatmentPBSDex2hDex6hDex24hTime oftreatment (h)0C2 624C2 624C2 624C2 624Dexa Dexa Dexa Dexa0PBS 5m<strong>in</strong> Iso 5m<strong>in</strong>TreatmentCDexa2 6 242 6 24β 2 ARβ-act<strong>in</strong>
β2AR <strong>signal<strong>in</strong>g</strong> can be modulated byhormones/drugs and contribute <strong>to</strong> enhancepathological bone lossWT miceβ2AR -/- miceSNSAdrß 2Adrß 2GCSNSAdrß 2Adrß 2OsteoblastOsteoblastBone formationBone resorption
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