1998 Fiscal Year Final Research Report Summary
Analyses on the growth factors which are involed in the development of ossification of the spinal ligaments
| Project/Area Number |
09671472
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Chiba University |
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Principal Investigator |
YAMAZAKI Masashi Chiba University, Chiba University Hospital, Assistant, 医学部附属病院, 助手 (50281712)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Sumio Chiba University, School of Medicine, Associate Professor, 医学部, 助教授 (10143273)
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| Project Period (FY) |
1997 – 1998
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| Keywords | ossification of the spinal ligaments, / growth factors, / osteogenesis, / bone cell biology, / immunohistochenistry, / molecular biology, / molecular genetics |
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| Research Abstract |
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.
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[Publications] Kon, T., Yamazaki, M., Tagawa, M., Goto, S., Terakado, A., Moriya, H., Fujimura, S.: "Bone morphogenetic protein-2 stimulates differentiation of cultured spinal ligament cells from patients with ossfication of the posterior longitudinal ligament." Calcif.Tissue Int. 60. 291-296 (1997)
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[Publications] Kobayashi, K., Yamazaki, M., Honda, T., Goto, K., Moriya, H., Fujimura, S.: "Effects of insulin-like growth factor 1 and basic fibroblast growth factor on DNA synthesis and collagen production of cultured anterior cruciate ligament cells." J.Orthop.Sci.2. 349-356 (1997)
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[Publications] Goto, K., Yamazaki, M., Tagawa, M., Goto, S., Kon, T., Moriya, H., Fujimura, S.: "Involvement of Insulin-like growth factor I in development of ossification of the posterior longitudinal ligament of the spine." Calcif.Tisssue.Int.62. 158-165 (1998)
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[Publications] Yamazaki, M., Majeska, R.J., Nakajima, F., Ogasawara, A., Moriya, H., Einhorn, T.A.: "Spatial and temporal distribution of CD44 and osteopontin in fracture callus." J.Bone and Joint Surg.(Br). (in press).
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