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Expression And Sinificance Of Metalloprpteinase-10 In The Nucleus Gelationosus And The Fibrous Ring Of Intervertebral Disc Degeneration

Posted on:2007-03-25Degree:MasterType:Thesis
Country:ChinaCandidate:Q WangFull Text:PDF
GTID:2144360182492141Subject:Surgery
Abstract/Summary:PDF Full Text Request
PrefaceThe degenerated nucleus gelatinosus has been considered as the pathologic base of many lumbar vertebral diseases and the mechanism is not clear now. . Many studies have indicated that the contents and the activity of the MMPs have a relationship with the degenerated nucleus gelatinosus.The intervertebral disc is composed of nucleus pulposus , fibrous ring and cartilage end - plate. The nucleus pulposus ' s water content is 80%. With the aging, the water content of the nucleus pulposus will decrease, then the tens of the nucleus gelatinosus will decrease and the intervertebral disc will be thinning. When the activity of the intervertebral disc cell decrease, the balance of the synthesis and degradation of the matrix will be broken, the intervertebral disc begin to degenerating.MMPs is a proteinase which is the key enzyme of degrading the extracellular matrix (ECM). That the human's intervertebral disc's protein contents have the same N - extremity with the protein of the cartilage matrix hints the MMPs perhaps produce a market effect during the nucleus gelatinosus degenerating.The MMPs mainly concentrate in the macrophage , collagenoblast and the cartilage cell ( nucleus gelatinosus and the fibrous ring). When the intervertebral disc damaged , the blood vessel invasion phenomenon will occur, that will activate the MMPs leading to the increasing of the matrix degradated. The macrophage can secrete the MMPs that can accelerate the degradation, so the fibrous ring will be weaken, and then the fibrous ring cleavage. The exodus disc willform the granulation tissue inflamed, when more granulation tissue inflamed produce the posterior - longitudinal fascia will nipt, the aggravate the degenaratingThe collagen of intervertebral disc 80% is type I and type II . Both exist together harmoniously and together function for maintain the exertive important function of the mechanics characteristic of intervertebral disc . The MMP - 10 can affect the I , II collagen , and activate to mainly degrade the MMPS , make collagen to take place to degeneration with elastin after degradation, cause the structure strength descend, solubility increace. Collagen occuring degeneration to make the fibrous ring weak, under outside force easily occur the fibrous ring break, elastin occurs degenrating to make intervertebral disc's elasticcity lower, affecting to be buffer by the machine power, through long -term repeatedly, easiest take place the fibrous ring break. In addition, the MMP -10 can also decline to solve many proteoglycan. After intervertebral disc degenerating their close cooperation lose, thus causing the fibrous ring break and the intervertebral disk hernia.Currently the local and the abroad all made the research of intervertebral disc degenarating and the MMPs to some degree, but the correlation of intervertebral disc degenarating and the MMPs is not yet be reported . This topic experiment by determining expression of the MMP - 10 in intervertebral disc verify the MMP - 10 function during the intervertebral disc degenarating , make us to have the further- understanding to the degenerated intervertebral disc , also provide the further reference for the mechanism of the degenerated intervertebral discMaterial and MethodsWe randomly Select 70 degenerated intervertebral disc samples and 15 non - degenerated intervertebral disc samples in the second affiliated hospital of CMU (2003 -2005) . all the sample has been divided into the normal group, protrude type, exodus type and liberation type, we replace monoanti with he PBS liquid as the negative control, go to get material, fix, embed and slice respectively, hematoxylin counterstain and the MMP - 10 immunohistochemis-tryand and the MMP -10 HE dyeing,the normal regulations HE dye, observing the expression of the positive cell under the microscope, measuring the positive cell rate. All data adopts the examination ofyResultsIn experiment group the MMP - 10 positive rate is 27% - 83% , average 50. 8%. In the control group the MMP -10 positive rate is 3% -32% , average 16.9%. The former is is obvious and high in the latter, its difference has a highly signiflcanc( the t is worth to 6.418, P <0.01). In the experiment group the MMP - 10 positive rate of the exodus type and liberation type obviously are higher than that of protrude type, its difference has a highly signiflcanc has a highly significanc ( the t worth is 23.113 , P<0.01) . The exodus type and liberation type has no significanc ( ( the t.is worth to 0.181, P >0.05)DiscussionThe degenerated nucleus gelatinosus has been considered as the pathologic base of many lumbar vertebral diseases and the mechanism is not clear now. . Many studies have indicated that the contents and the activity of the MMPs have a relationship with the degenerated nucleus gelatinosus. The intervertebral disc is composed of nucleus pulposus ^ fibrous ring and cartilage end -plate. The nucleus pulposus ' s water content is 80%. With the aging, the water content of the nucleus pulposus will decrease, then the tens of the nucleus gelatinosus will decrease and the intervertebral disc will be thinning. When the activity of the intervertebral disc cell decrease, the balance of the synthesis and degradation of the matrix will be broken, the intervertebral disc begin to degenerating. MMPs is a proteinase which is the key enzyme of degrading the extracellular matrix ( ECM) . That the humans intervertebral discs protein contents have the same N - extremity with the protein of the cartilage matrix hints the MMPs perhaps produce a market effect during the nucleus gelatinosus degenerating. Currently the local and the abroad all made the research of intervertebral disc degenarating and the MMPs to some degree, but the correlation of intervertebral disc degenarating and the MMPs is not yet be reported . This topic experiment by deter-mining expression of the MMP - 10 in intervertebral disc verify the MMP - 10 function during the intervertebral disc degenarating , make us to have the further understanding to the degenerated intervertebral discln this experiment, MMP -10 immunohistochemical stain is at the kytoplasm ,and highly expressed in the degenerated nucleus pulposus.Among them, in 70 examples of degenerated intervertebral disc , the highly expression of the MMP - 10 is 39 samples(55.7% ) . In 36 examples of protrude type degenerated intervertebral disc , the highly expression of the MMP - 10 is 5 samples (13.9% ) . In 39 examples of exodus type and liberation type degenerated intervertebral disc , the highly expression of the MMP - 10 is 34 samples (87.1% ). But in the control group, the expression of the MMP - 10 is 0 sample. So there must be a. close relationship between the expression of the MMP -10 and the degree of the degenerated intervertebral disc. The MMPs mainly is to degrading the ECM. The degradation of the ECM is determined by the activity of the MMPs, but the MMP - 10 that is one of enzyme that degrading the ECM, whose substrate is extensive, can degrade many proteoglycan^laminin^Fibronec-tin and UK W\V\VI type collagen and can activate other MMPs, (it can activate the pro MMP - 1 and pro MMP -8 completely). Another one important aspect, the MMP - 10 can degrade some proteins, such as the collagen III^IV^ V ,gelatin, nidogen, laminin - 1, proteoglycans and elastin etc. MMP - 10 can also remove the N^C extremity of the I N H >,HI collagen , acting as the procollagen peptidase. So, with the more degrading of ECM than the synthesis of the ECM and the degenerating of the intervertebral disc, the MMP —10 s expression in the intervertebral disc increase obviously high.In 24 examples of exodus type and 15 examples of liberation type degenerated intervertebral disc , the highly expression of the MMP - 10 is 87. 5% and 86.7% respectively. In 36 examples of protrude type degenerated intervertebral disc , the highly expression of the MMP - 10 is 5 samples (13. 9% ). It has been reported that main concentration of MMPs is in the macrophage, collageno-blast and the cartilage cell ( the fibrous ring and nucleus pulposus). Moreover, the more granulation tissue , the more stronger MMPs stain and the more weaker matrix proteoglycan stain. Many persons think macrophage releasing the cytokineto promote the above cell synthesizing MMPs. Therefore, we presume that the posterior longitudinal ligament is broken because the enzyme degradating the collagen and weaking its structure . The exodus disc will form the granulation tissue inflamed, when more granulation tissue inflamed produce the posterior - longitudinal fascia will rupt, the aggravate the degenarating, then appearing with the clinical symptom and MRI image.The collagen of intervertebral disc 80% is type I and type II. Both exist together harmoniously and together function for maintain the exertive important function of the mechanics characteristic of intervertebral disc . PG is the main giant molecule structure in the intervertebral disc , iit& quality and content determine the strength of the intervertebral disc and have a important significant to maintain the properties of the nucleus pulposus . The collagen is also the main giant molecule , which constitute of the intercellular framework ,. the intervertebral disc contain the collagen I^II^IV\IX^XI. The MMP - 10 can affect the I ^ H collagen , and activate to mainly degrade the MMPS , which remove the NNC extremity of the INII ^ III collagen acting as the procollagen peptidase , make collagen and elastin to take place to degeneration with elastin after degradation, cause the structure strength descend, solubility increace. Collagen occuring degeneration to make the fibrous ring weak, under outside force easily occur the fibrous ring break, elastin occurs degenrating to make intervertebral discs elastic-city lower, affecting to be buffer by the machine power, through long - term repeatedly, easiest take place the fibrous ring break. In addition, the MMP - 10 can also decline to solve many proteoglycan. The close cooperation of the PG, collagen and the elastin in the intervertebral disc is the base of the good mechanics function of the intervertebral disc' The PG can counteract to the compressive stress,. The collagen can counteract to the tensile stress, and the elastin can amortize the mechanical force. After intervertebral disc degenerating their close cooperation lose, thus causing the fibrous ring break and the intervertebral disk hernia. Above all the MMP -10 can change the structure ^function and content of the biomacromolecule such as the PG, collagen and the elastin , thus MMP -10 act the role during the intervertebral disc degenerating.ConclusionThis topic experiment by determining expression of the MMP - 10 in inter-vertebral: disc verify the MMP -10 s promotion function during the intervertebral disc degenaratmg , at the same time the MMP -10 perhaps is one of the reason which leading to the degenerating of the intervertebral disc progressively.
Keywords/Search Tags:Intervertebral disc, MMPs, MMP -10, Degeneration
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