Recombinant human fibroblastic growth factor-2 with soluble tumor necrosis factor receptor-1 facilitates fracture repair in rats with type 2 diabetes mellitus
- VernacularTitle:重组人成纤维细胞生长因子2联合可溶性肿瘤坏死因子Ⅰ型受体蛋白促进2型糖尿病大鼠骨折修复
- Author:
Zhendong LIU
;
Jielin ZHONG
;
Yi XU
;
Jie MIAO
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2007;11(32):6505-6508
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: It has been reported that type 1 diabetes mellitus can result in impairments of bone regeneration and repair, and local injection of fibroblastic growth factor-2 (FGF-2) can obviously promote fracture healing, but its effect on type 2 diabetes mellitus is still unclear.OBJECTIVE: To observe the effects of recombinant human fibroblastic growth factor-2 (rhFGF-2) combined with soluble tumor necrosis factor receptor-1 (sTNF-R1) on impaired bone regeneration and repair in type 2 diabetes mellitus.DESTGN: A randomized controlled trial.SETTING: Department of Orthopaedics, the Third Xiangya Hospital of Central South University.MATERIALS: Twenty male Zucker diabetic fatty rats (ZDF/Gemi-fa/fa), 10 weeks of age, were purchased from Charles River Laboratory. rhFGF-2 was obtained from Orquest Incorporation; sTNF-R1 protein (PEG-r-metHu-sTNF-R1) was provided by Amgen Incorporation.METHODS: This experiment was finished in the central lab of the Third Xiangya Hospital of Central South University from September to November in 2006. ①Grouping: The 20 rats were randomly assigned into treated group (n =10)and control group (n =10). ② Experimental methods: All rats were examined for body mass, blood glucose, glycosuria and glycosemia. One week later, all the rats underwent the standard DO protocol, including placement of the external fixators and osteotomies to the left tibia. Distraction was initiated in the following morning (one day latency) at 0.2 mm b.I.d. (0.4 mm per day) and continued for 14 days. During surgery, all the rats received an injection of either rhFGF-2(25 mg/kg) for the treated group, or physiological saline (25 mg/kg) for the control group, into the hematoma of the osteotomic gap. The sTNF-R1 (8 mg/kg) or the same. Amount of saline was subcutaneously injected into the treated and control rats respectively every other day for 14 days. Evaluation: The serum biochemical indexes, amount of bone formation and number of proliferative cells in the distraction gaps were determined.MAIN OUTCOME MEASURES: Biochemical indexes, amount of bone formation and number of proliferative cells in the distraction gaps.RESULTS: All the 20 rats were involved in the final analysis of results. ①The blood glucose, glucosuria, ketonuria,serum levels of insulin and osteocalcin were not obviously different between the treated group and control group (P ＞0.05). ② The area and density of mineralization of the distraction gaps, and the endosteal and peristeal new bone formation in the treated group were all obviously higher than those in the control group (P ＜ 0.05-0.01). The number and percentage of the positive cells of proliferating cell nuclear antigen (PCNA) in the distraction gaps were obviously higher in the treated group than in the control group (P ＜ 0.05-0.01).CONCLUSION: The local application of rhFGF-2 combined with sTNF-R1 can enhance bone formation by increasing the proliferation during distraction osteogenesis in ZDF rats. The combination of rhFGF-2 and sTNF-R1 may be an effective treatment for type 2 diabetic patients with fracture healing problem.
