INVOLVEMENT OF INSULIN-LIKE-GROWTH-FACTOR-I IN DEVELOPMENT OF OSSIFICATION OF THE POSTERIOR LONGITUDINAL LIGAMENT OF THE SPINE

In order to investigate the pathogenesis of ossification of the poster ior longitudinal Ligament (OPLL) of the spine, we examined the distrib ution of insulin-like growth factor I(IGF-I) in the posterior longitud inal ligaments of OPLL patients, and analyzed the effects of IGF-I on the cultured spinal ligament cells. For that purpose we established ei ght varieties of OPLL and non-OPLL cell Lines obtained from spinal lig aments of corresponding patients, respectively. In contrast to non-OPL L cases, all the OPLL cases were histologically shown to contain round -shaped cartilage-like cells in the transitional region from preossify ing to ossifying ligaments, and these cells were strongly stained with an antibody for IGF-I. In the vicinity of preossifying cartilaginous tissues, Ligament cells also had a rod-like appearance and were positi ve for IGF-I immunohistochemically. The effects of IGF-I on cultured s pinal ligament cells were assayed by alkaline phosphatase (AP) activit y, DNA synthesis, and the amounts of collagen produced. The number of OPLL cell lines that increased AP activity, responding to IGF-I irresp ective of 1,25(OH)(2)D-3, was significantly larger than that of non-OP LL cell Lines, although IGF-I stimulated DNA and procollagen type I ca rboxyl-terminal peptide synthesis in most of both OPLL and non-OPLL ce ll lines. These data demonstrate the dominant expression of IGF-I in t he posterior longitudinal ligaments of OPLL patients, and suggest that IGF-I preferentially induces osteogenic differentiation in OPLL cells rather than in non-OPLL cells. IGF-I, therefore, may be involved in t he local ossification process of spinal ligaments observed in OPLL pat ients.