| Title |
Homozygous Dkk1 Knockout Mice Exhibit High Bone Mass Phenotype Due to Increased Bone Formation
|
|---|---|
| Published in |
Calcified Tissue International, November 2017
|
| DOI | 10.1007/s00223-017-0338-4 |
| Pubmed ID | |
| Authors |
Michelle M. McDonald, Alyson Morse, Aaron Schindeler, Kathy Mikulec, Lauren Peacock, Tegan Cheng, Justin Bobyn, Lucinda Lee, Paul A. Baldock, Peter I. Croucher, Patrick P. L. Tam, David G. Little |
| Abstract |
Wnt antagonist Dkk1 is a negative regulator of bone formation and Dkk1 (+/-) heterozygous mice display a high bone mass phenotype. Complete loss of Dkk1 function disrupts embryonic head development. Homozygous Dkk1 (-/-) mice that were heterozygous for Wnt3 loss of function mutation (termed Dkk1 KO) are viable and allowed studying the effects of homozygous inactivation of Dkk1 on bone formation. Dkk1 KO mice showed a high bone mass phenotype exceeding that of heterozygous mice as well as a high incidence of polydactyly and kinky tails. Whole body bone density was increased in the Dkk1 KO mice as shown by longitudinal dual-energy X-ray absorptiometry. MicroCT analysis of the distal femur revealed up to 3-fold increases in trabecular bone volume and up to 2-fold increases in the vertebrae, compared to wild type controls. Cortical bone was increased in both the tibiae and vertebrae, which correlated with increased strength in tibial 4-point bending and vertebral compression tests. Dynamic histomorphometry identified increased bone formation as the mechanism underlying the high bone mass phenotype in Dkk1 KO mice, with no changes in bone resorption. Mice featuring only Wnt3 heterozygosity showed no evident bone phenotype. Our findings highlight a critical role for Dkk1 in the regulation of bone formation and a gene dose-dependent response to loss of DKK1 function. Targeting Dkk1 to enhance bone formation offers therapeutic potential for osteoporosis. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 21 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 19% |
| Researcher | 3 | 14% |
| Other | 2 | 10% |
| Student > Master | 2 | 10% |
| Professor | 1 | 5% |
| Other | 2 | 10% |
| Unknown | 7 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 29% |
| Medicine and Dentistry | 4 | 19% |
| Agricultural and Biological Sciences | 2 | 10% |
| Sports and Recreations | 1 | 5% |
| Engineering | 1 | 5% |
| Other | 0 | 0% |
| Unknown | 7 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 November 2017.
All research outputs
#15,483,026
of 23,007,887 outputs
Outputs from Calcified Tissue International
#1,356
of 1,780 outputs
Outputs of similar age
#207,169
of 330,777 outputs
Outputs of similar age from Calcified Tissue International
#26
of 39 outputs
Altmetric has tracked 23,007,887 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,780 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.9. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
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We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.