ABSTRACT
Objective To explore the effect of T140 on SDF-1 and MMPs levels through targeted blocking SDF-1/CXCR4 signaling pathway , and to investigate the function of T140 to prevent from cartilage degeneration. Methods Thirty-six 9-month-old male healthy Hartley guinea pigs were divided into three groups: experimental group(group A,n = 12),experimental control group(group B,n = 12) and blank control group (group C,n = 12). In the 2nd,4th,6th,8th,10th,12th week, the levels of SDF-1 in serum were quantified with ELISA. In the 12th week, mRNA levels of MMP-3,MMP-9 and MMP-13 in articular cartilages were measured with RT-PCR. Results The serum levels of SDF-1 of the group A decreased gradually but increased in group B and C. Group A had a statistical significance compared with group B and C at the same time point (P< 0.05).The mRNA levels of MMPs in group A were lower than group B and C (P < 0.05). Conclusion T140 could block the SDF-1/CRCR4 signaling pathway and decrease the secretion of SDF-1 and mRNA expression levels of MMPs and reduce the cartilage degeneration.
ABSTRACT
Objective To explore the impact of blockade of SDF-1/CXCR4 signaling pathway by T140 on degradation of typeⅡ collagen in human articular cartilage and to define the mechanism of action of T140. Methods 144 pieces of cartilage (Mankin score of 0 or 1) were obtained from osteoarthritis patients undergoing total knee replacement ( OA cartilage group) and 144 pieces of cartilage (Mankin score of 0 or 1) were obtained from patients receiving traumatic amputation (normal cartilage group). Each group was treated with SDF-1 of 100 ng/mL, then divided into three subgroups A, B, and C. The cartilage tissue in each group was cultured in the nutrient solution containing of T140, MAB310, or SDF-1 (1 000 nmol/L) for 48 or 96 hours. RT-PCR was used to detect expression of typeⅡcollagen mRNA in the cartilage tissue. Results Level of type Ⅱcollagen mRNA was markedly higher in subgroup A than in subgroup B and subgroup C at the same group and the same time (P <0.05). The expression level of type Ⅱcollagen mRNA at the same time and in the same subgroup of OA cartilage group were lower than that in normal cartilage group (P < 0.05). Conclusions SDF-1 induces degradation of typeⅡcollagen in human articular cartilage thruogh the SDF-1/CXCR4 signaling pathway. T140 can block the SDF-1/CXCR4 signaling pathway and reduce the degradation of type II collagen.
ABSTRACT
Objective To explore the repair result of full-thickness cartilage defects in diannan small-ear pig by bone mesenchymal stem cells (BMSCs) transferred with both transforming growth factor-β3(TGF-β3) and bone morphogenetic protein-2(BMP-2) gene mediated by adenovirus vector and combined with deminerized bone matrix (DBM). Methods 32 full-thickness defects from 16 knees of 8 pigs were randomly divided into 4 groups in the experiments. In group A, the animals′ lateral femoral condyle of right knee joint was repaired with DBM and BMSC infected with both Ad-TGF-β3 and Ad-BMP-2. In group B, the medial femoral condyle of right knee joint was repaired with DBM and BMSC without infection. In group C, the lateral femoral condyle of left knee joint was repaired with DBM. And the group D is control group. Morphology and histology were observed 2, 4, 8 and 12 weeks after operation. Results 12 weeks after operation, the whole defects were repaired in group A, HE staining showed typical cartilaginous structure in the repaired area. In group D, defects were not repaired but filled with fibrous tissue. The O′driscoll scores were 15.65 ± 0.11 (group A), 11.33 ± 0.22 (group B), 6.13 ± 0.15 (group C) and 5.08 ± 0.15 (group D). There was significant difference among the groups (P < 0.05). Conclusions The new type of tissue engineering scaffold that DBM combined with BMSCs transfected with both Ad-BMP-2 and Ad-TGF-β3 could induce cartilage regeneration and repair the defects.