Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone
Joint Authors
Fowlkes, John L.
Thrailkill, Kathryn M.
Bunn, R. Clay
Cockrell, Gael E.
Morris, Lindsey
Kahn, C. Ronald
Nyman, Jeffry S.
Wahl, Elizabeth C.
Lumpkin, Charles K.
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-05-18
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture.
These clinical observations, paralleled by animal models of T1D, suggest that the insulinopenia of T1D has a deleterious effect on bone.
To further examine the action of insulin signaling on bone development, we generated mice with an osteoprogenitor-selective (osterix-Cre) ablation of the insulin receptor (IR), designated OIRKO.
OIRKO mice exhibited an 80% decrease in IR in osteoblasts.
Prenatal elimination of IR did not affect fetal survival or gross morphology.
However, loss of IR in mouse osteoblasts resulted in a postnatal growth-constricted phenotype.
By 10–12 weeks of age, femurs of OIRKO mice were more slender, with a thinner diaphyseal cortex and, consequently, a decrease in whole bone strength when subjected to bending.
In male mice alone, decreased metaphyseal trabecular bone, with thinner and more rodlike trabeculae, was also observed.
OIRKO mice did not, however, exhibit abnormal glucose tolerance.
The skeletal phenotype of the OIRKO mouse appeared more severe than that of previously reported bone-specific IR knockdown models, and confirms that insulin receptor expression in osteoblasts is critically important for proper bone development and maintenance of structural integrity.
American Psychological Association (APA)
Thrailkill, Kathryn M.& Bunn, R. Clay& Lumpkin, Charles K.& Wahl, Elizabeth C.& Cockrell, Gael E.& Morris, Lindsey…[et al.]. 2014. Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone. Journal of Diabetes Research،Vol. 2014, no. 2014, pp.1-9.
https://search.emarefa.net/detail/BIM-1040327
Modern Language Association (MLA)
Thrailkill, Kathryn M.…[et al.]. Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone. Journal of Diabetes Research No. 2014 (2014), pp.1-9.
https://search.emarefa.net/detail/BIM-1040327
American Medical Association (AMA)
Thrailkill, Kathryn M.& Bunn, R. Clay& Lumpkin, Charles K.& Wahl, Elizabeth C.& Cockrell, Gael E.& Morris, Lindsey…[et al.]. Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone. Journal of Diabetes Research. 2014. Vol. 2014, no. 2014, pp.1-9.
https://search.emarefa.net/detail/BIM-1040327
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1040327