Expression of cartilage-derived morphogenetic protein in human intervertebral discs and its effect on matrix synthesis in degenerate human nucleus pulposus cells.
BACKGROUND
Loss of intervertebral disc (IVD) matrix and ultimately disc height as a result of 'degeneration' has been implicated as a major cause of low back pain (LBP). The use of anabolic growth factors as therapies to regenerate IVD matrix, hence restoring disc height and thus reversing degenerative disc disease, has been suggested. Cartilage-derived morphogenetic protein (CDMP) is a growth factor which stimulates proteoglycan production in chondrocyte-like cells and thus could be a useful growth factor for LBP therapies. However, little is known about the expression of CDMP or its receptor in human IVD, nor its effects on human disc cells.


METHODS
Using immunohistochemistry we investigated the localisation of CDMP in non-degenerate and degenerate human IVDs. Additionally, we investigated the effect of CDMP on aggrecan and type II collagen gene expression and proteoglycan synthesis in nucleus pulposus (NP) cells derived from degenerate IVDs.


RESULTS
We demonstrated that CDMP 1 and 2 were expressed in the non-degenerate and degenerate IVD, particularly in cells of the NP. A small decrease in the number of CDMP 1 and 2 immunopositive cells was seen with degeneration. Treatment of human NP cells, (derived from degenerate IVD), with CDMP showed an increase in aggrecan and type II collagen gene expression and increased production of proteoglycan (GAGs).


CONCLUSIONS
The data suggests that CDMP may be a useful growth factor to stimulate proteoglycan production in the human degenerate IVD and hence the repair of the extracellular matrix.
Le Maitre
Christine L
CL
Biomedical Research Centre, Biosciences, Faculty of Health and Wellbeing, Sheffield Hallam University, City Campus, Owen Building, Howard Street, Sheffield, S1 1WB, UK. c.lemaitre@shu.ac.uk
Freemont
Anthony J
AJ
Hoyland
Judith A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000096:biosynthesis; D024043:Collagen Type II / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006025:Glycosaminoglycans / Q000096:biosynthesis; D055428:Growth Differentiation Factor 5 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053674:Aggrecans; D024043:Collagen Type II; C525893:GDF5 protein, human; D006025:Glycosaminoglycans; D055428:Growth Differentiation Factor 5