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The Expression Of Chondromodulin-Ⅰ In The Adult Degenerative Intervertebral Discs

Posted on:2012-09-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:X LiFull Text:PDF
GTID:1114330335481918Subject:Surgery
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Background Previous study of our laboratory showed that there were different protein expression levels between the convex and concave sides of the intervertebral discs endplate cartilage in AIS patients. The key proteins which express on the convex or concave side exclusively may involved in the progress of the AIS. Recent study showed that morphologic disc degeneration was accelerated about 20 years in scoliosis versus physiological ageing. The result indicated that the key proteins may also involved in the progress of intervertebral disc degeneration. Chondromodulin-I (ChM-I) is one of the key proteins which express on the convex side exclusively. ChM-I can stimulate the proliferation of chondrocytes and maintain the avascularity and anti-angiogenic properties of normal cartilage. It is also associated with the progress of osteoarthritis, valvular heart diseases and tumor. Yet the role of ChM-I in intervertebral disc degeneration is still unkown.Objectives1. To investigate the expression of ChM-I in the intervertebral disc cells.2. To investigate the effect of bFGF on the expression of ChM-I in the intervertebral disc cells.3. To examine the expression of ChM-I and to correlate its expression with the degree of disc degeneration.4. To discus the role of ChM-I in the disc degeneration.Methods1. Three IVDs obtained from patients in the treatment of disc degenerative disease were used for cell culture. ChM-I expression in IVD cells was examined by using RT-PCR and Western blot.2. The effect of bFGF on the expression of ChM-I was assessed by real-time PCR and Western blot respectively.3. Twenty-eight human IVD tissues were obtained from patients in the surgical treatment of disc degenerative disease at different stage of degeneration according to MRI.6 IVD tissues removed from patients with metastatic spinal tumor were used as normal control. The expression of ChM-I determined by immunohistochemical analyses was correlated with MRI degeneration grade.Results1. RT-PCR and Western blot examination showed that ChM-I expressed in both adult degenerative anulus fibrosus cells and nucleus pulposus cells.2. The mRNA and protein expression of ChM-I were both down-regulated by administration of bFGF with dose-dependent way(P<0.05)3. Immunohistochemical analyses showed the number of ChM-I-expression cells in human IVD tissues was significantly elevated in advanced stages of IVD(grade III, IV, V) degeneration compared with those in normal control(P<0.05)Conclusions1. ChM-I mRNA and protein are expressed in IVD cells.2. The expression of ChM-I is down-regulated by administration of bFGF.3. The expression of ChM-I in discs with advanced stage of degeneration is elevated compared with those with nondegeneration which indicate that the expression of ChM-I is upregulated through a defense mechanism against the degenerative process of intervertebral disc.
Keywords/Search Tags:Intervertebral disc, Molecular biology, Chondromodulin, Intervertebral disc degeneration,human
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