BONE MORPHOGENETIC PROTEIN-2 STIMULATES DIFFERENTIATION OF CULTURED SPINAL LIGAMENT CELLS FROM PATIENTS WITH OSSIFICATION OF THE POSTERIOR LONGITUDINAL LIGAMENT

Ossification of the posterior longitudinal ligament (OPLL) of the spin e is characterized by heterotopic bone formation occurring in spinal l igament, causing severe compression myelopathy. In order to investigat e the mechanism of OPLL development, we isolated spinal ligament cells from OPLL patients as well as non-OPLL patients, and established 10 O PLL cell lines and 7 non-OPLL cell lines, respectively. We analyzed th e effects of bone morphogenetic protein-2 (BMP-2) on these cells with respect to alkaline phosphatase (AP) activity, DNA synthesis, and coll agen production. BMP-2 caused a significant increase of AP activity in 4 OPLL cell lines, whereas the activity did not change in any non-OPL L cells. Among OPLL cells, BMP-2 stimulated DNA synthesis in four cell lines and procollagen type I carboxyl-terminal peptide (PICP) synthes is in five cell lines. Some non-OPLL cells also responded to BMP-2, as there was an increase of DNA synthesis in three cell lines and PICP s ynthesis in one cell line. These data collectively indicate that BMP-2 preferentially induces osteogenic differentiation in OPLL cells rathe r than in non-OPLL cells. OPLL cells, therefore, exhibit a different r esponse to BMP-2 than non-OPLL cells, suggesting that the expression o f BMP receptor(s) and/or the signal transduction initiated by BMP-2 in the spinal ligament cells of OPLL patients somewhat deviate from thos e in normal spinal ligament cells. Such abnormal characteristics of OP LL cells as described here provide some clues to the clarification of the pathogenesis of OPLL.