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A Research On The Effect Of Leptin On The Hypertrophy Of Chondrocytes In Vertebrae And Limb Growth Plates

Posted on:2018-06-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:K B JiangFull Text:PDF
GTID:1364330590955113Subject:Surgery
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Objective: To investigate the differential regulation of leptin on the hypertrophy of vertebral growth plate(VGP)and tibial growth plate(TGP)chondrocytes.Background: Leptin plays an important role in mediating chondrogenesis of limb growth plate.Previous studies suggest that the expression of Ob-Rb,the gene that encodes leptin receptors,is vertebral and appendicular region-specific and the specific role of leptin on the development of VGP and TGP may lead to the deformity in spine.Methods:We injected leptin to 5 ob/ob mice and injected PBS to 5 ob/ob and WT mice.At organic and tissue level,we compared the region-specific effect of leptin on the chondrogenesis of vertebral and limb by length measurement and toluidine blue staining.We then generated primary cultures of TGP and VGP chondrocytes of 5 WT mice.By co-culturing the primary cells with different concentrations of leptin in vitro at 24 h and 48 h,we analyzed proliferation of the primary chondrocytes from TGP and VGP.We further measured expression of chondrogenic-related genes in these cells that had been incubated with different doses of leptin by Real-time PCR.Results: Leptin-deficient mice of 8-week-old had shorter femur and longer vertebral lengths than the wild type mice and the proportion of the hypertrophic zone in VGP is larger in ob/ob mice than in wild type mice,with the opposite results in TGP.The abnormal phenomenon can be fixed by the leptin injection totally or partially.In primary chondrocyte cultures,leptin inhibited VGP chondrocyte proliferation and hypertrophy.Sox9 and Runx2 mRNA were downregulated by leptin in a dose-dependent manner.In contrast,leptin stimulated the proliferation and chondrogenic hypertrophy in a complicated manner.Conclusion: Leptin exerts a stimulatory effect on the growth of the long bone but an inhibitory effect on the spine growth.The mechanism may be the region-specific effect of leptin on the growth plate chondrogenic hypertrophy.The ongoing study will shed light on the regulatory mechanisms of leptin in bone development and then we will have a better understanding of the pathogenesis of spine deformity.The results will provide us with a new idea in treating spine deformity.
Keywords/Search Tags:leptin, chondrogenic hypertrophy, vertebral growth plate, tibial growth plate, chondrocyte
PDF Full Text Request
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