RGD Reference Report - Osteocrin is a specific ligand of the natriuretic Peptide clearance receptor that modulates bone growth. - Rat Genome Database

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Osteocrin is a specific ligand of the natriuretic Peptide clearance receptor that modulates bone growth.

Authors: Moffatt, P  Thomas, G  Sellin, K  Bessette, MC  Lafreniere, F  Akhouayri, O  St-Arnaud, R  Lanctot, C 
Citation: Moffatt P, etal., J Biol Chem. 2007 Dec 14;282(50):36454-62. Epub 2007 Oct 19.
RGD ID: 8553616
Pubmed: PMID:17951249   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M708596200   (Journal Full-text)

Osteocrin (Ostn) is a recently discovered secreted protein produced by cells of the osteoblast lineage that shows a well conserved homology with members of the natriuretic peptide (NP) family. We hypothesized that Ostn could interact with the NP receptors, thereby modulating NP actions on the skeleton. Ostn binds specifically and saturably to the NP peptide receptor-C (NPR-C) receptor with a Kd of approximately 5 nM with no binding to the GC-A or GC-B receptors. Deletion of several of the residues deemed important for NP binding to NPR-C led to abolition of Ostn binding, confirming the presence of a "natriuretic motif." Functionally, Ostn was able to augment C-type natriuretic peptide-stimulated cGMP production in both pre-chondrocytic (ATDC5) and osteoblastic (UMR106) cells, suggesting increased NP levels due to attenuation of NPR-C associated NP clearance. Ostn-transgenic mice displayed elongated bones and a marked kyphosis associated with elevated bone cGMP levels, suggesting that elevated natriuretic peptide activity contributed to the increased bone length possibly through an increase in growth plate chondrocyte proliferation. Thus, we have demonstrated that Ostn is a naturally occurring ligand of the NPR-C clearance receptor and may act to locally modulate the actions of the natriuretic system in bone by blocking the clearance action of NPR-C, thus locally elevating levels of C-type natriuretic peptide.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NppaRatreceptor guanylyl cyclase signaling pathway acts_upstream_of_or_withinIDA PMID:17951249MGI 
NppcRatreceptor guanylyl cyclase signaling pathway acts_upstream_of_or_withinIDA PMID:17951249MGI 

Objects Annotated

Genes (Rattus norvegicus)
Nppa  (natriuretic peptide A)
Nppc  (natriuretic peptide C)


Additional Information