Analyses on the growth factors which are involed in the development of ossification of the spinal ligaments

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In this study, we analyzed the involvement of growth factors in the development of ossification of the spinal ligaments from the standpoint of cell biology, molecular biology and molecular genetics.We first evaluated the direct actions of growth factors on the spinal ligament cells from OPLL patients. The results showed that BMP2 stimulated osteogenic differentiation of the cells. Their activities for matrix production and proliferation were enhanced by TGF-beta1 and bFGF, respectively. IGF-1 increased both growth and matrix production of the cells. We then examined the combinatory effects of growth factors on the cells. Regarding osteogenic differentiation, the action of BMP2 on the cells was enhanced by IGF-l, but was suppressed by bFGF.By detecting the PCNA antigen immunohistochemically, we evaluated the growth activity of cells in the spinal ligament tissues of OPLL patients. The results showed that the spinal ligament cells of OPLL patients have acquired elevated growth activities not only at the vertebral edge levels but also at the mid-vertebral levels. Such altered phenotypes of the ligament cells of OPLL patients seem to contribute to the onset and progression of OPLL.Previous reports have shown that COL11A2 is one of the candidate genes for the OPLL development, We analyzed the pattern of gene expression for type XI collagen during osteogenesis using in situ hybridization. Although type XI collagen had been recognized to be specific for cartilage tissues, the results showed that considerable amounts of mRNA for type XI collagen was also expressed in non-cartilaginous tissues.We have analyzed twy mice as an animal model for OPLL.In this study, we identified the genetic locus of twy mice using a positional candidate-gene approach. In this mice, a missence mutation is present in the gene coding Npps (nucleotide pyrophosphatase). This suggests that functional abnormalities of Npps cause heterotopic ossification in the spinal ligaments.