Bone morphogenetic protein-2 stimulates differentiation of cultured spinal ligament cells from patients with ossification of the posterior longitudinal ligament

Calcif Tissue Int. 1997 Mar;60(3):291-6. doi: 10.1007/s002239900231.


Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by heterotopic bone formation occurring in spinal ligament, causing severe compression myelopathy. In order to investigate the mechanism of OPLL development, we isolated spinal ligament cells from OPLL patients as well as non-OPLL patients, and established 10 OPLL cell lines and 7 non-OPLL cell lines, respectively. We analyzed the effects of bone morphogenetic protein-2 (BMP-2) on these cells with respect to alkaline phosphatase (AP) activity, DNA synthesis, and collagen production. BMP-2 caused a significant increase of AP activity in 4 OPLL cell lines, whereas the activity did not change in any non-OPLL cells. Among OPLL cells, BMP-2 stimulated DNA synthesis in four cell lines and procollagen type I carboxyl-terminal peptide (PICP) synthesis 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 synthesis in one cell line. These data collectively indicate that BMP-2 preferentially induces osteogenic differentiation in OPLL cells rather than in non-OPLL cells. OPLL cells, therefore, exhibit a different response to BMP-2 than non-OPLL cells, suggesting that the expression of BMP receptor(s) and/or the signal transduction initiated by BMP-2 in the spinal ligament cells of OPLL patients somewhat deviate from those in normal spinal ligament cells. Such abnormal characteristics of OPLL cells as described here provide some clues to the clarification of the pathogenesis of OPLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / drug effects
  • Alkaline Phosphatase / metabolism
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / pharmacology
  • Bone Morphogenetic Proteins / physiology*
  • Cell Differentiation / drug effects
  • Cells, Cultured / drug effects
  • DNA / biosynthesis
  • DNA / drug effects
  • Humans
  • Longitudinal Ligaments / cytology*
  • Longitudinal Ligaments / drug effects
  • Ossification of Posterior Longitudinal Ligament / etiology
  • Ossification of Posterior Longitudinal Ligament / pathology
  • Ossification of Posterior Longitudinal Ligament / physiopathology*
  • Peptide Fragments / biosynthesis
  • Peptide Fragments / drug effects
  • Procollagen / biosynthesis
  • Procollagen / drug effects
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor beta*
  • Transforming Growth Factors / pharmacology
  • Transforming Growth Factors / physiology*


  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Peptide Fragments
  • Procollagen
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • procollagen type I carboxy terminal peptide
  • recombinant human bone morphogenetic protein-2
  • Transforming Growth Factors
  • DNA
  • Alkaline Phosphatase