| To date, the involvement of proteinases in the degeneration of intervertebral discs has been restricted to investigations of matrix metalloproteinase. Other proteinases may also be involved in this process. Cathepsin D is an ubiquitous asp-artyl endoproteinase that is distributed in lysosomes and plays an important role in protein degradation and the generation of bio - active proteins.SubjectiveFrom Jun,2002to Nov, 2003, 30 cases with lumbar disc protrusion disease and 10 cases of thoracic - lumbar broken were chosen. All the cases were from the department of orthopedics of No. 1 hospital of China Medical University.MethodsParaffin - embedded sections of normal and degenerated lumbar intervertebral disc tissue collected at the time of surgery (40 discs from 40 patients) were immunohistochemically stained with antibodies for cathepsin D. Furthermore, mRNA of cathepsin D of 23 samples from two group was detected by RT - PCR to determine the relationship of cathepsin D and the pathomechanism of lumbar intervertebral disc degeneration.ResultsHematoxylin and eosin staining revealed obvious signs of degeneration indegenerated sections. Cathepsins D was immunolocalized in disc cells at various sites exhibiting degeneration. But few cells were positive for cathepsin D in anu-lus fibrosus that maintained the lamellar structure of collagen fibers which characterized normal intervertebral discs. Furthermore, mRNA of cathepsin D was upregulated in degenerated disc tissue compared to the normal disc tissue, was detected by RT - PCR.DiscussionDegeneration involves biologic changes, which are most pronounced in the nucleus, and gross structural changes, which are most evident in the annulus and endplate. Common structural changes include radial fissures, circumferential clefts and rim tears in the annulus, inward buckling of the inner annulus, increased radial bulging of the annulus, reduced disc height, endplate defects, and vertical bulging of the endplates into the adjacent vertebral bodies.The problem of whether disc degeneration usually is initiated by mechanical or biologic factors is important because it affects strategies of research on the prevention and treatment of disc - related back pain. Currently, there is considerable interest in identifying biochemical and metabolic abnormalities in degenerated disc tissues.Disk degeneration is associated with gross alterations in intrinsic structure, changes in biochemical characteristics, and increased apoptosis of resident chondrocytes . The many factors that influence disk degeneration include genetic factors , age, disk nutrition, and production in some cases of matrix - degradation products . Proteolysis reactions in response to autocrine or paracrine stimulation by cytokines may participate in the pathophysiology of disk degeneration.The familys of MMPs and TIMPs play the key role in the process of ECM degradation. In spite of MMPs, other proteinases may also contribute to this changes. Recent research indicate that cathepsin D has this function.One significant difference between MMPs and cathepsins is their optimal pH. Unlike MMPs, which have an optimal pH that is approximately neutral, cathepsins have their optimal activity in an acid environment. The intervertebraldisc are the largest tissue in the human body that do not contain a vascular system, with diffusion the major mechanism whereby nutrients are supplied to the intervertebral disc. Moreover, oxygen concentration in the discs drops as the region of measurement gets closer to the center of the disc. Therefore, an increase of lactic acid concentration occurs, which is thought to result in a lowering of the pH, because of anaerobic glycolysis by disc cells.Here we have shown the existence of cathepsin D in normal an degenerated intervertebral disc tissue, which strongly suggests the involvement of this proteases in intervertebral disc degeneration. Several different proteinases may be involved appropriately in matrix destruction depending on the pH during the...
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