Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments

Bone. 2003 Oct;33(4):475-84. doi: 10.1016/s8756-3282(03)00204-7.


Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Mechanical stress, which acts on the posterior ligaments, is thought to be an important factor in the progression of OPLL. To elucidate this mechanism, we investigated the effects of in vitro sinusoidal cyclic stretch (120% peak to peak, at 1 Hz) on cultured spinal ligament cells derived from OPLL and non-OPLL patients. The mRNA expressions of alkaline phosphatase (ALP), osteopontin, bone morphogenetic protein (BMP)-2, BMP-4, and BMP receptors as well as ALP activity in cell layers and production of BMPs into the conditioned medium were significantly increased by cyclic stretch in OPLL cells, whereas no change was observed in non-OPLL cells. A stretch-activated Ca(2+) channel blocker, Gd(3+), the voltage-dependent L-type Ca(2+) channel blockers diltiazem and nifedipine, and Ca(2+)-free medium suppressed stretch-induced ALP activity, which suggests a role of Ca(2+) influx in the signal transduction of mechanical stress to the osteogenic response of OPLL cells. Our study provides first evidences that mechanical stress plays a key role in the progression of OPLL through the induction of osteogenic differentiation in spinal ligament cells and the promotion of the autocrine/paracrine mechanism of BMPs in this lesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Base Sequence
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein Receptors
  • Bone Morphogenetic Proteins / biosynthesis*
  • Bone Morphogenetic Proteins / genetics
  • Calcium Channels, L-Type / genetics
  • Cell Differentiation
  • Cells, Cultured
  • DNA / genetics
  • Gene Expression
  • Humans
  • Longitudinal Ligaments / metabolism*
  • Longitudinal Ligaments / pathology*
  • Ossification of Posterior Longitudinal Ligament / etiology
  • Ossification of Posterior Longitudinal Ligament / metabolism*
  • Ossification of Posterior Longitudinal Ligament / pathology*
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteogenesis / physiology*
  • Osteopontin
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Growth Factor / genetics
  • Sialoglycoproteins / genetics
  • Stress, Mechanical
  • Transforming Growth Factor beta*


  • BMP2 protein, human
  • BMP4 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Calcium Channels, L-Type
  • L-type calcium channel alpha(1C)
  • RNA, Messenger
  • Receptors, Growth Factor
  • SPP1 protein, human
  • Sialoglycoproteins
  • Transforming Growth Factor beta
  • Osteopontin
  • DNA
  • Bone Morphogenetic Protein Receptors
  • Alkaline Phosphatase