RGD Reference Report - Dickkopf-1 regulates bone formation in young growing rodents and upon traumatic injury. - Rat Genome Database

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Dickkopf-1 regulates bone formation in young growing rodents and upon traumatic injury.

Authors: Li, X  Grisanti, M  Fan, W  Asuncion, FJ  Tan, HL  Dwyer, D  Han, CY  Yu, L  Lee, J  Lee, E  Barrero, M  Kurimoto, P  Niu, QT  Geng, Z  Winters, A  Horan, T  Steavenson, S  Jacobsen, F  Chen, Q  Haldankar, R  Lavallee, J  Tipton, B  Daris, M  Sheng, J  Lu, HS  Daris, K  Deshpande, R  Valente, EG  Salimi-Moosavi, H  Kostenuik, PJ  Li, J  Liu, M  Li, C  Lacey, DL  Simonet, WS  Ke, HZ  Babij, P  Stolina, M  Ominsky, MS  Richards, WG 
Citation: Li X, etal., J Bone Miner Res. 2011 Nov;26(11):2610-21. doi: 10.1002/jbmr.472.
RGD ID: 6907379
Pubmed: PMID:21773994   (View Abstract at PubMed)
DOI: DOI:10.1002/jbmr.472   (Journal Full-text)

The physiological role of Dickkopf-1 (Dkk1) during postnatal bone growth in rodents and in adult rodents was examined utilizing an antibody to Dkk1 (Dkk1-Ab) that blocked Dkk1 binding to both low density lipoprotein receptor-related protein 6 (LRP6) and Kremen2, thereby preventing the Wnt inhibitory activity of Dkk1. Treatment of growing mice and rats with Dkk1-Ab resulted in a significant increase in bone mineral density because of increased bone formation. In contrast, treatment of adult ovariectomized rats did not appreciably impact bone, an effect that was associated with decreased Dkk1 expression in the serum and bone of older rats. Finally, we showed that Dkk1 plays a prominent role in adult bone by mediating fracture healing in adult rodents. These data suggest that, whereas Dkk1 significantly regulates bone formation in younger animals, its role in older animals is limited to pathologies that lead to the induction of Dkk1 expression in bone and/or serum, such as traumatic injury.

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Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of ossification  IMP 6907379 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dkk1  (dickkopf WNT signaling pathway inhibitor 1)

Genes (Mus musculus)
Dkk1  (dickkopf WNT signaling pathway inhibitor 1)

Genes (Homo sapiens)
DKK1  (dickkopf WNT signaling pathway inhibitor 1)


Additional Information