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.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.
Takegami
Kenji
K
Department of Biochemistry, Rush University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA.
An
Howard S
HS
Kumano
Fumio
F
Chiba
Kazuhiro
K
Thonar
Eugene J
EJ
Singh
Kern
K
Masuda
Koichi
K
D000464:Alginates; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D019765:Chondroitin ABC Lyase / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000187:drug effects*; D020723:Glucuronic Acid; D006025:Glycosaminoglycans / Q000378:metabolism; D006603:Hexuronic Acids; D066298:In Vitro Techniques; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism; D007404:Intervertebral Disc Chemolysis; D011509:Proteoglycans / Q000096:biosynthesis / Q000187:drug effects; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000464:Alginates; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D006025:Glycosaminoglycans; D006603:Hexuronic Acids; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C013786:A73025; D020723:Glucuronic Acid; D019765:Chondroitin ABC Lyase