The Etiology Of Adolescent Idiopathic Scoliosis(AIS):the Association Of Microfibril Proteins With The Development Of Scoliosis

Purpose:Adolescent idiopathic scoliosis (AIS) is a deformity of the spine which develops in otherwise healthy children during the growth spurt. We still do not know how the scoliotic deformity starts and progresses, although lots of research has been done on scoliosis. Increasing research demonstrate that microfibrills are closely associated with the development of adolescent idopathetic scoliosis(AIS). Intervertebral disc, which is the connective structure between adjacent vertebral bodies, also plays important roles in the progress of scoliosis. The purpose of our is to study the distribution of microfibrills in the intervertebral disc, and compare the differences between AIS patients and normal controls. Additionally, we also plan to study how, where and when the scoliotic deformity starts and progresses, through the establishment of3D model of developmental scoliosis.Method:1, Isolate normal bovine tail disc and study the distribution of Fibrillin-1, Fibrillin-2and LTBP-2in bovine tail disc through immunofluoresence stain. Study the associations among Fibrillin-1, Fibrilin-2and LTBP-2in different parts of bovine tail disc. Study the distribution of fibrillin-1and fibrillin-2in normal human intervertebral disc and compare the results with thoes from bovine disc;2, Using immunofluorescence stain and immunohistology technique to study the distributions of fibrillin-1, fibrillin-2and BMP-2in discs of nomral human and patients with scoliosis;3, Do micro-ct scan of the transgenic mouse, which can develop scoliosis, and their wild type controls at different time points during their growth. Estabish3D reconstruction based on the data from micro-ct scan, and mearsure the parameters related to growth, then make comparision between transgenic mouse and their wild type controls. At the same time, we also study the distribution of elastin in spinal tissues at different time points during their growth.Results:In bovine intervertebral disc, the association between Fibrillin-I and Fibrillin-2are region-specific. In OAF, they are filamentous and co-localized. In IAF, they formed nebulous structure and closely co-localized in perricellular territory. While in interterritorial matrix, Fibrillin-1lessly distributed. In NP, rare Fibrillin-1was distributed in the interterritorial matrix, while Fibrillin-2was still filamentous and parallel. In perricellular territory, they formed nebulous structure and closely co-localized. As to LTBP-2, its morphology and distribution are very similar to those of Fibrillin-1in evey part of bovine disc. The results of human disc indicate that the distribution of Fibrilin-1and Fibrillin-2is very similar to those in bovine disc.The results from human samples indicate that the distributions of Fibrillin-1, Fibrillin-2and BMP-2in discs of scoliotic patients become more sparse and chaos compared with normal discs. The model of distribution for BMP-2is very similar to that of Fibrillin-1and LTBP-2in bovine disc. Because of the huge individual differences in humans and insufficient sample size, especially the lackness of normal human disc, we still can not confirm wheher there are differences in the distribution and amount of microfibrills between scolitotic patients and normal controls, or not.The3D model could be reconstructed quickly by using micro-CT, Image J and Osirix. Using Osirix, we could measure many parameters, inluding the length of ribs. The reason that KY mouse presents less scoliosis and more kyphosis may due to the character of four feet. Our research also shows that the degeneration of disc is more serious in KY mouse than in BDL mouse.Conclusions:1Region-specific distribution of microfibrills in different parts of bovine disc.2The microfibrills in annulus fibrosus of disc of patients with scoliosis are more sparse and disturbed than those in normal controls.3The3D model could be reconstructed quickly by using micro-CT, Image J and Osirix.4The reason that KY mouse presents less scoliosis and more kyphosis may due to the character of four feet.5The degeneration of disc is more serious in KY mouse than in BDL mouse with growth.