[Role of PGI2 in ectopic bone formation of spinal ligaments]

Ossification of the posterior longitudinal ligament (OPLL) is characterized by ectopic bone formation in the spinal ligaments. It has been suggested some role of mechanical stress in the progression of OPLL. Differential display RT-PCR was carried out to identify the genes participating in OPLL. A cDNA fragment corresponding to PGI2 synthase was highly expressed in OPLL cells compared to non-OPLL cells. To examine the effect of mechanical stress on the PGI2 synthase expression, cells were subjected to cyclic stretch and PGI2 synthase expression was assessed by quantitative RT-PCR. Cyclic stretch induced a time-dependent increase in PGI2 synthase in OPLL cells but not in non-OPLL cells. The increase in PGI2 synthase was diminished by SQ22536, a potent adenylate cyclase inhibitor. Cyclic stretch also induced PGI2 production. Beraprost and dibutyryl cAMP increased the mRNA expression of alkaline phosphatase (ALP) as a marker for osteogenic differentiation in OPLL cells, whereas no change was observed in non-OPLL cells. Beraprost- and stretch-induced increases in ALP expressions were inhibited by SQ22536. These data suggest that PGI2 synthase activated by mechanical stress plays a key role in the progression of OPLL, at least in part through the osteogenic differentiation in spinal ligament cells via the PGI2/cAMP system.