Osteogenic protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after chondroitinase ABC-induced in vitro chemonucleolysis

Spine J. 2005 May-Jun;5(3):231-8. doi: 10.1016/j.spinee.2004.11.001.

Abstract

Background context: Chondroitinase ABC (C-ABC) is used in chemonucleolysis to degrade, with great specificity, the chondroitin sulfate and dermatan sulfate chains of proteoglycans (PGs). A recent study showed that osteogenic protein-1 (OP-1) is very effective in stimulating the production and formation of the extracellular matrix by rabbit intervertebral disc cells.

Purpose: To test the hypothesis that the repair of the extracellular matrix of the intervertebral disc after chemonucleolysis by C-ABC can be stimulated by exposure to a low dose of a growth factor, OP-1.

Study design: An alginate bead cell culture system was used to monitor the effects of OP-1 on the repair of damaged matrices after in vitro chemonucleolysis with C-ABC.

Methods: Rabbit nucleus pulposus (NP) or annulus fibrosus (AF) cells cultured for 2 weeks in alginate gel were briefly exposed to low concentrations of C-ABC and then cultured in the presence or absence of OP-1. The control group was cultured without enzyme treatment for the same period in the absence of OP-1. At each time point, the contents of DNA and proteoglycan accumulation and proteoglycan synthesis were measured.

Results: NP or AF cells cultured in alginate beads, which were digested with C-ABC and then treated with OP-1, recover PG content more rapidly than those cultured in the absence of OP-1. The major contributor to the superior matrix repair in the cells treated with OP-1 was an up-regulation of proteoglycan synthesis.

Conclusions: OP-1 was effective in stimulating matrix repair by NP and AF cells after their matrices were nearly totally depleted of sulfated glycosaminoglycans. The use of OP-1 after chemonucleolysis might help the disc to regain biomechanical strength, weakened by enzyme digestion, by stimulating matrix metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alginates
  • Animals
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / pharmacology*
  • Chondroitin ABC Lyase / therapeutic use*
  • Extracellular Matrix / drug effects*
  • Glucuronic Acid
  • Glycosaminoglycans / metabolism
  • Hexuronic Acids
  • In Vitro Techniques
  • Intervertebral Disc / cytology*
  • Intervertebral Disc / metabolism
  • Intervertebral Disc Chemolysis
  • Proteoglycans / biosynthesis
  • Proteoglycans / drug effects
  • Rabbits
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Alginates
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Glycosaminoglycans
  • Hexuronic Acids
  • Proteoglycans
  • Transforming Growth Factor beta
  • A73025
  • Glucuronic Acid
  • Chondroitin ABC Lyase