OBJECTIVE: To explore the synergistic effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on the growth of bone tissue. METHODS: A total of 36 rabbits were randomly divided into 4 groups with 9 rabbits (18 sides of the anterior limb) in each group, including group A,B,C, and D. For all rabbits 1.0 cm bone defects was created in both sides of the radius. These bone defect regions were implanted with corresponding composites: group A with calcium phosphate cement (CPC) only, group B with CPC/bFGF, group C with CPC/VEGF while group D with both bFGF and VEGF. At the 3rd, 6th, and 12th week after the operation, 6 specimens from each group were randomly selected. The effects were partly assessed by X-ray film examination, bone mineral density (BMD) measurements, biomechanical test and histological observation. RESULTS: X-ray showed that at the 12th week the bone defects in group D were completely repaired with CPC generally degraded,whereas bone defects in group B and C were only basically repaired. BMD measurements showed that at the 12th week the BMD of group D was significantly higher than that of group B and C (P < 0.05). Biomechanical testing(at the 12th week) showed that the maximum bending load of group D was significantly higher than that of group B and C (P < 0.05). Histological observation indicated that at the 12th week, woven bone had become mature lamellar bone in group D. At the same time, the normal relation of cortical bone and marrow had resumed, and so had the normal structure of trabecula. However, the recanalization of bone marrow cavity could not be seen in group B and C. CONCLUSION These 3 kinds of composite: CPC/bFGF, CPC/VEGF and CPC/ bFGF+VEGF can promote the growth of bone tissue and speed up the repair of bone defects. The composite of CPC/bFGF+VEGF is better than the other two composites in promoting the growth of bone tissues, indicating that bFGF and VEGF have a synergistic effect on the growth of bone tissue.
Animals ; Bone Cements ; Calcium Phosphates ; administration & dosage ; Drug Synergism ; Female ; Fibroblast Growth Factor 2 ; administration & dosage ; Implants, Experimental ; Male ; Rabbits ; Radius ; injuries ; surgery ; Random Allocation ; Vascular Endothelial Growth Factor A ; administration & dosage

ObjectiveTo investigate the effect and mechanism of cordycepin in inhibiting fat infiltration after rotator cuff injuries in rats by regulating the Wnt/β-catenin signaling pathway， providing a theoretical basis for clinical treatment of rotator cuff injuries. MethodsFifty SPF-grade female SD rats were used in this study， with 10 randomly selected as the blank group. A rotator cuff injury repair model was established by supraspinatus tendon and suprascapular nerve compression. The successfully modeled rats were randomized into model and low-dose （20 mg·kg^-1）， medium-dose （40 mg·kg^-1）， and high-dose （80 mg·kg^-1） cordycepin groups. After 6 weeks of treatment， the gait analysis was performed to assess the limb function in rats. Oil red O staining and Masson staining were employed to observe pathological changes in the muscle tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum. Immunohistochemistry （IHC） was employed to detect the expression of peroxisome proliferator-activated receptor γ （PPARγ） and CCAAT/enhancer-binding protein α （C/EBPα）， which are markers of adipogenesis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of Wnt3a， Wnt10b， and β-catenin. ResultsCompared with the blank group， the model group showed decreases in stride length and paw print area （P<0.01）， an increase in ratio of wet muscle mass reduction and a decrease in muscle fiber cross-sectional area （P<0.05）， and decreased ratios of fat infiltration area and collagen fiber area （P<0.01）. Additionally， the model group showed elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， up-regulated protein levels of PPARγ and C/EBPα （P<0.01）， and down-regulated mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. Compared with the model group， the low-， medium-， and high-dose cordycepin groups showed increases in stride length and paw print area （P<0.01）， a decrease in ratio of wet muscle mass reduction and an increase in muscle fiber cross-sectional area （P<0.05）， and increases in ratios of fat infiltration area and collagen fiber area （P<0.05， P<0.01）. In addition， cordycepin lowered the serum levels of IL-1β， IL-6， and TNF-α （P<0.05， P<0.01）， down-regulated the protein levels of PPARγ and C/EBPα （P<0.01）， and up-regulated the mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. ConclusionCordycepin can improve the limb function， alleviate rotator cuff muscle atrophy， fat infiltration， and fibrosis， and inhibit inflammation in rats by regulating the Wnt/β-catenin signaling pathway.