Expression of PPARgamma and Cbfalpha1 mRNA in bone marrow cells in Type 2 diabetic rats and its correlation with impaired fracture healing.
OBJECTIVE
To investigate the relationship between impaired fracture healing and the expression of peroxisome proliferator activated-receptor gamma (PPARgamma) and core binding factor alpha 1 (Cbfalpha1) mRNA in the bone marrow of Type 2 diabetic rats.


METHODS
Thirty male Sprague-Dawley rats were divided into a control group (n=15, normal diet) and an experiment group (n=20, high fat and sucrosum diet). After 8 weeks, one eyeball was culled for blood collection. The experiment group was intraperitoneally injected with streptozotocin and the control group received citrate buffer. After another 2 weeks, the other eyeball was culled again to collect blood. The model of distraction osteogenesis in the left tibias of the rats was established. After 14 days, we sacrificed all the rats and collected the blood and left tibias. Both femurs were harvested with germ free. We observed the callus formation in the distraction gap by X-ray and the formation of primary matrix front and microcolumn by histological examination. We observed adipocytes in adjacent bone marrow of left tibia and computed the percentage of adipocytes accounting for the area of bone cavity. We measured the expression of PPARgamma and Cbfalpha1 mRNA in femurs marrow by RT-PCR.


RESULTS
In the experimental rats, the level of triglyceride was obviously elevated (P<0.01), so was the total cholesterol (P<0.05), while the level of fasting blood glucose and serum insulin did not obviously differ (P>0.05) after 8 weeks. The level of fasting blood glucose and triglyceride was obviously elevated (P<0.01), and so was the total cholesterol (P<0.05), while the level of serum insulin was not obviously different in the experiment group after 10 and 12 weeks. Callus formation in the distraction gap was obviously diminished by X-ray in the experimental rats. The array of microcolumn formation was disordered and the area of primary matrix front was catachromasis in the controls by histology examination. The number of adipocytes in both the bone marrow and the percentage of adipocyte accounting for the area of bone cavity increased (P<0.01) in the experiment group. In the experiment group, the expression of PPARgamma mRNA was up-regulated (P<0.05) while Cbfalpha1 mRNA was down-regulated (P<0.05) in double femur marrow.


CONCLUSIONS
Increased expression of PPARgamma mRNA and decreased expression of Cbfalpha1 mRNA in the bone marrow may cause impaired fracture healing in rats with Type 2 diabetes.
Xu
Yi
Y
First Department of Orthopaedics, Central Hospital of Changsha, Changsha, China.
Chen
Xianli
X
Liu
Baoheng
B
Chou
Ke
K
Liu
Zhendong
Z
Deng
Jianliang
J
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D017102:Fracture Healing; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013978:Tibial Fractures / Q000150:complications / Q000503:physiopathology
D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma; D012333:RNA, Messenger