A novel rat model for the study of deficits in bone formation in type-2 diabetes.
BACKGROUND
There is evidence to suggest that impairment in bone formation and/or turnover is associated with the metabolic abnormalities characteristic of type-2 diabetes mellitus. However, bone regeneration/repair in type-2 diabetes has not been modeled. Using Zucker Diabetic Fatty (ZDF) rats (a model of type-2 diabetes) for tibial distraction osteogenesis (DO), we hypothesized that bone formation within the distraction gap would be impaired.


METHODS
Rats were examined for body weight, glycosuria, and glycosemia to confirm the diabetic condition during the study. The rats received placement of the external fixators and osteotomies on the left tibia. Distraction was initiated the following day at 0.2 mm twice a day and continued for 14 days. The lengthened tibiae were harvested and distraction gaps were examined radiographically and histologically.


RESULTS
We found significant reduction in new bone formation in the distraction gaps of the ZDF rats, both radiographically and histologically, compared to lean rats. We found a decrease in a marker of cellular proliferation in the distraction gaps and increased adipose volume in adjacent bone marrow of the ZDF rats.


CONCLUSIONS
Our findings suggest that this model might be used to study the contributions of leptin resistance, insulin resistance and/or hyperglycemia to impaired osteoblastogenesis in vivo.
Liu
Zhendong
Z
Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA.
Aronson
James
J
Wahl
Elizabeth C
EC
Liu
Lichu
L
Perrien
Daniel S
DS
Kern
Phillip A
PA
Fowlkes
John L
JL
Thrailkill
Kathryn M
KM
Bunn
Robert C
RC
Cockrell
Gael E
GE
Skinner
Robert A
RA
Lumpkin
Charles K
CK
D000818:Animals; D015519:Bone Density; D001861:Bone Regeneration / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008954:Models, Biological; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker; D013977:Tibia / Q000166:cytology / Q000378:metabolism / Q000473:pathology