Abstract:
:Parathyroid hormone (PTH), the major calcium-regulating hormone, and norepinephrine (NE), the principal neurotransmitter of sympathetic nerves, regulate bone remodeling by activating distinct cell-surface G protein-coupled receptors in osteoblasts: the parathyroid hormone type 1 receptor (PTHR) and the β(2)-adrenergic receptor (β(2)AR), respectively. These receptors activate a common cAMP/PKA signal transduction pathway mediated through the stimulatory heterotrimeric G protein. Activation of β(2)AR via the sympathetic nervous system decreases bone formation and increases bone resorption. Conversely, daily injection of PTH (1-34), a regimen known as intermittent (i)PTH treatment, increases bone mass through the stimulation of trabecular and cortical bone formation and decreases fracture incidences in severe cases of osteoporosis. Here, we show that iPTH has no osteoanabolic activity in mice lacking the β(2)AR. β(2)AR deficiency suppressed both iPTH-induced increase in bone formation and resorption. We showed that the lack of β(2)AR blocks expression of iPTH-target genes involved in bone formation and resorption that are regulated by the cAMP/PKA pathway. These data implicate an unexpected functional interaction between PTHR and β(2)AR, two G protein-coupled receptors from distinct families, which control bone formation and PTH anabolism.
journal_name
Proc Natl Acad Sci U S Aauthors
Hanyu R,Wehbi VL,Hayata T,Moriya S,Feinstein TN,Ezura Y,Nagao M,Saita Y,Hemmi H,Notomi T,Nakamoto T,Schipani E,Takeda S,Kaneko K,Kurosawa H,Karsenty G,Kronenberg HM,Vilardaga JP,Noda Mdoi
10.1073/pnas.1109036109subject
Has Abstractpub_date
2012-05-08 00:00:00pages
7433-8issue
19eissn
0027-8424issn
1091-6490pii
1109036109journal_volume
109pub_type
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