title: Dickkopf-1 regulates bone formation in young growing rodents and upon traumatic injury.
abstract: 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.
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Mario
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authors.lastname: Grisanti
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Asuncion
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Tan
authors.forename: Denise
authors.initials: D
authors.lastname: Dwyer
authors.forename: Chun-Ya
authors.initials: CY
authors.lastname: Han
authors.forename: Longchuan
authors.initials: L
authors.lastname: Yu
authors.forename: Jae
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authors.forename: Edward
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authors.lastname: Kurimoto
authors.forename: Qing-Tian
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authors.lastname: Niu
authors.forename: Zhaopo
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authors.lastname: Geng
authors.forename: Aaron
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authors.lastname: Winters
authors.forename: Tom
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authors.lastname: Horan
authors.forename: Shirley
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authors.lastname: Steavenson
authors.forename: Frederick
authors.initials: F
authors.lastname: Jacobsen
authors.forename: Qing
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authors.lastname: Chen
authors.forename: Raj
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authors.lastname: Haldankar
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authors.lastname: Lavallee
authors.forename: Barbara
authors.initials: B
authors.lastname: Tipton
authors.forename: Mark
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authors.lastname: Daris
authors.forename: Jackie
authors.initials: J
authors.lastname: Sheng
authors.forename: Hsieng S
authors.initials: HS
authors.lastname: Lu
authors.forename: Kristi
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authors.lastname: Daris
authors.forename: Rohini
authors.initials: R
authors.lastname: Deshpande
authors.forename: Eliane G
authors.initials: EG
authors.lastname: Valente
authors.forename: Hossein
authors.initials: H
authors.lastname: Salimi-Moosavi
authors.forename: Paul J
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authors.lastname: Kostenuik
authors.forename: Ji
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authors.lastname: Li
authors.forename: Min
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authors.lastname: Liu
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Li
authors.forename: David L
authors.initials: DL
authors.lastname: Lacey
authors.forename: W Scott
authors.initials: WS
authors.lastname: Simonet
authors.forename: Hua Zhu
authors.initials: HZ
authors.lastname: Ke
authors.forename: Philip
authors.initials: P
authors.lastname: Babij
authors.forename: Marina
authors.initials: M
authors.lastname: Stolina
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ominsky
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000503:physiopathology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004967:Estrogens / Q000172:deficiency; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D019138:Antibodies, Blocking; C501127:Dkk1 protein, mouse; C531384:Dkk1 protein, rat; D004967:Estrogens; D036341:Intercellular Signaling Peptides and Proteins