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Calcitonin controls bone formation by inhibiting the release of sphingosine
1-phosphate from osteoclasts
#MMPMID25333900
Keller J
; Catala-Lehnen P
; Huebner AK
; Jeschke A
; Heckt T
; Lueth A
; Krause M
; Koehne T
; Albers J
; Schulze J
; Schilling S
; Haberland M
; Denninger H
; Neven M
; Hermans-Borgmeyer I
; Streichert T
; Breer S
; Barvencik F
; Levkau B
; Rathkolb B
; Wolf E
; Calzada-Wack J
; Neff F
; Gailus-Durner V
; Fuchs H
; de Angelis MH
; Klutmann S
; Tsourdi E
; Hofbauer LC
; Kleuser B
; Chun J
; Schinke T
; Amling M
Nat Commun
2014[Oct]; 5
(?): 5215
PMID25333900
show ga
The hormone calcitonin (CT) is primarily known for its pharmacologic action as an
inhibitor of bone resorption, yet CT-deficient mice display increased bone
formation. These findings raised the question about the underlying cellular and
molecular mechanism of CT action. Here we show that either ubiquitous or
osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased
bone formation. CT negatively regulates the osteoclast expression of Spns2 gene,
which encodes a transporter for the signalling lipid sphingosine 1-phosphate
(S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype
is normalized by deletion of the S1P receptor S1P3. Finally, pharmacologic
treatment with the nonselective S1P receptor agonist FTY720 causes increased bone
formation in wild-type, but not in S1P3-deficient mice. This study redefines the
role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic
molecule in vivo and provides evidence for a pharmacologically exploitable
crosstalk between osteoclasts and osteoblasts.
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