Effects of growth differentiation factor-5 on the intervertebral disc--in vitro bovine study and in vivo rabbit disc degeneration model study.
METHODS
In vitro studies on the effects of recombinant human growth and differentiation factor-5 (rhGDF-5) on matrix metabolism of bovine intervertebral disc cells and an in vivo study on the effect of rhGDF-5 in the rabbit anular puncture model.


OBJECTIVE
To determine the reparative capacity of rhGDF-5 on the intervertebral disc.


BACKGROUND
The in vitro and in vivo effects of rhGDF-5, a crucial protein in the developing musculoskeletal system, on repair of the degenerated intervertebral disc remain unidentified.


METHODS
In vitro, bovine nucleus pulposus and anulus fibrosus cells were cultured with or without rhGDF-5 (100 or 200 ng/mL). On days 7, 14, and 21, the contents of deoxyribonucleic acid and proteoglycan, and the synthesis of proteoglycan and collagen were assessed. In vivo, 16 adolescent New Zealand white rabbits received anular punctures in 2 lumbar discs. Four weeks later, phosphate buffered saline or rhGDF-5 (10 ng, 1 and 100 mug) was injected into the nucleus pulposus. The rabbits were followed up for 16 weeks for disc height, magnetic resonance imaging, and histologic grading.


RESULTS
In vitro, rhGDF-5 increased the deoxyribonucleic acid and proteoglycan contents of both cell types significantly after day 14. rhGDF-5 at 200 ng/mL significantly stimulated proteoglycan synthesis (nucleus pulposus: +138%, anulus fibrosus: +24%) and collagen synthesis (nucleus pulposus: +95%, anulus fibrosus: +23%) at day 21. In vivo, the injection of rhGDF-5 resulted in a restoration of disc height, improvement of magnetic resonance imaging scores, and histologic grading scores with statistical significance (P < 0.05-0.001).


CONCLUSIONS
A single injection of rhGDF-5 has a reparative capacity on intervertebral discs, presumably based on its effects to enhance extracellular matrix production in vitro.
Chujo
Takehide
T
Orthopedic Surgery, Rush Medical College at Rush University Medical Center, Chicago, IL, USA.
An
Howard S
HS
Akeda
Koji
K
Miyamoto
Kei
K
Muehleman
Carol
C
Attawia
Mohamed
M
Andersson
Gunnar
G
Masuda
Koichi
K
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology* / Q000627:therapeutic use*; D002417:Cattle; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055428:Growth Differentiation Factor 5; D006801:Humans; D007403:Intervertebral Disc / Q000187:drug effects* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D013122:Spinal Diseases / Q000188:drug therapy* / Q000473:pathology
D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5