Associations of age-related expression changes of peroxisome proliferator-activated receptor gamma and core binding factor alpha 1 in bone marrow cells with age-related fracture healing impaimont in rats / 中国组织工程研究

ABSTRACT

BACKGROUND: It was reported that the reason why the fracture healing become more and more difficult with the increasing age may be associated with the varied gene regulation of bone marrow mesenchymal stem cells differentiation into osteoblast and lipoblast. However, the exact mechanism under it remains poorly understood.OBJECTIVE: To explore the association of the age-related changes on expression of peroxisome proliferator-activated receptor γ (PPARγ) and core binding α1 (Cbfα1) with the age-relatad fracture healing impairment, we studied the expression changes of PPARγ and Cbfα1 during aging fracture healing.DESIGN, TIME AND SETTING: A randomized control animal trial was performed in the Third Xiangya Hospital of Central South University between October 2007 and Febuary 2008. MATERIALS Six male SD rats of 3 months and the other six of 23 months, randomly-selected, were divided into two groups the old experiment group (23 months) and the young control group (3 months). METHODS: Transverse osteotomies on the middle-upper parts of left tibiae were performed to the rats, with the self-made extemal mini-fixator implanted there simultaneously. Tractions were taken twice a day (0.2 mm/d) for 14 days from day 2 till day 15 post operation. On day 15 post operation, rats were sacrificed to harvest left tibea samples. MAIN OUTCOME MEASURES: Both imaging examination and histological observation were performed to the fractures of rats. The PPARγ and Cbfα1 expression were detected with reverse transcription-polymerase chain reaction (RT-PCR) technique. RESULTS: All samples were involved in the results analyses. The imaging examination showed that many osteotylus generated between the broken ends of fractures in the young control group; that the bone formation of the young control group was much better than that of the old experiment group. The histological observation showed that large amounts of osteotylus growth occurred to every animal in the young control group and their membrane bone formation was remarkable; comparatively, the osteotylus growth in the old group was weakened dramatically, and only fibrous joints were seen. The RT-PCR detection showed that differences of significance existed in both PPARγ and Cbfα1 mRNA expressions between the two groups, with the much higher Cbfol mRNA expression in the bone marrow of rats in the young group and the much higher PPARy mRNA expression in the bone marrow of rats in the old group.CONCLUSION: Rats of different ages show different fracture healing abilities, i.e. the higher ages, the lower fracture healing abilities. In addition, expressions of PPARγ and Cbfα1 in the bone marrow of rats alter with the increasing age, which indicates that there are certain associations between the changed expression level of the two factors and the fracture healing impartment.