Molecular events caused by cyclic stretch in spinal ligament cells from patients with ossification of the posterior longitudinal ligament

Abstract

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Although mechanical stress is thought to be an important factor in the progression of OPLL, the mechanism by which mechanical stress promotes the ossification of ligaments in OPLL is still unknown. Therefore, we investigated osteogenic responses induced by mechanical stress in OPLL cells and pathways required for transmitting mechanical signals in these processes. Cells obtained from spinal ligament tissues of OPLL and non-OPLL patients (NOP) were subjected to uni-axial cyclic stretch. Messenger RNA expressions of alkaline phosphatase (ALP) and osteopontin, bone morphogenetic protein-2 (BMP-2), and ALP activity in OPLL cells were significantly increased by cyclic stretch, whereas no change was observed in non-OPLL cells. Ca 2+ channel blockers suppressed stretch-induced ALP activity to resting state level. Furthermore, conditioned medium of OPLL cell cultures subjected to cyclic stretch increased the ALP activity of other OPLL cells. These results suggested that mechanical stress plays a key role in the progression of OPLL through the induction of osteogenic differentiation in ligament cells, Ca 2+ mobilization and promotion of the autocrine/paracrine mechanism of BMP-2 in this lesion.