BoneKEy Reports | BoneKEy Watch

β2 adrenergic receptor regulates the anabolic action of PTH in bone



DOI:10.1038/bonekey.2012.143

In osteoblasts, interactions between parathyroid hormone (PTH) and the parathyroid hormone type 1 receptor (PTHR), and between norepinephrine (NE) and the β2-adrenergic receptor (β2AR), regulate bone modeling. Intermittent (i) PTH therapy is used in osteoporosis to stimulate bone formation in order to increase bone mass and to reduce fracture risk. This study investigated how deficiency of β2AR might impact on i(PTH) treatment.

β2AR knockout mice and wild type mice showed very different responses to i(PTH) treatment. The former showed no changes in trabecular bone, whereas wild type mice showed a significant increase in bone formation as expected. This suggests that the β2AR is required for the osteoanabolic activity of i(PTH).

Further analysis revealed that interactions with the β2AR are required to stimulate expression of several iPTH target genes, including alkaline phosphatase (ALP), type I collagen a1 (Col1a1), bone sialoprotein (BSP), RANKL and osteoprotegerin (OPG). This is the first time that a functional interaction relevant to bone formation and resorption has been demonstrated between these two receptors.

Editor's comment: The interaction between the PTHR and the β2AR are unexpected as these receptors are from two distinct families. The data presented here agree with another recent study, which confirms that activation of β2AR via the sympathetic nervous system decreases bone formation and increases bone resorption during aging.


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