Expression of cathepsin K and matrix metalloproteinase 1 indicate persistent osteodestructive activity in long-standing ankylosing spondylitis.
BACKGROUND
Ankylosing spondylitis (AS) is a common, largely genetically determined, rheumatic disease that is characterised by spinal inflammation and new bone formation. However, the exact pathogenesis and pathology are still not clear.


OBJECTIVE
To analyse tissue obtained at spinal surgery by immunohistochemistry and compare the specimen of patients with AS to those with degenerative disc disease (DDD).


METHODS
Bony and soft tissue specimens of 30 patients with AS and 20 with DDD were obtained during spinal osteotomy from different anatomic regions including articular and spinous processes, interspinous ligaments and intervertebral disks. Immunohistolochemistry was performed with established markers for cathepsin K, matrix metalloproteinase (MMP)1, MMP3 and receptor activator for nuclear factor kappaB (RANK) ligand.


RESULTS
Cathepsin K and MMP1-positive cells were only observed in AS specimens. Cathepsin K-positive multinucleated cells were detected at articular processes adjacent to fibrous tissues. MMP1 was expressed in smaller mononuclear cells attached to bone. Invasion of bone by MMP1 cells was seen at entheseal sites. In the intervertebral disks, most mononuclear cells were cathepsin K-positive. Isolated cells expressing these matrix-degrading enzymes found in DDD never showed signs of invasion. No differences were found for MMP3 between AS and DDD. Clear expression of RANK ligand was only detected in one patient with AS.


CONCLUSIONS
Cathepsin K is strongly expressed in different regions of the spine in AS. Cathepsin K was mainly expressed by mononuclear cells, fibroblast-like cells and cells attached to bone and at sites of bone remodelling, suggestive of high osteoclastic activity. This supports the role of persistent inflammation in the pathogenesis of AS. How these changes relate to osteoproliferation remains to be determined.
Neidhart
M
M
World Health Organization Collaboratory Center for Molecular Biology, University Hospital Zürich, Zürich, Switzerland.
Baraliakos
X
X
Seemayer
C
C
Zelder
C
C
Gay
R E
RE
Michel
B A
BA
Boehm
H
H
Gay
S
S
Braun
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000201:enzymology; D008279:Magnetic Resonance Imaging; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D010010:Osteoclasts / Q000201:enzymology; D013122:Spinal Diseases / Q000201:enzymology / Q000473:pathology; D013167:Spondylitis, Ankylosing / Q000201:enzymology* / Q000473:pathology
D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D020781:Matrix Metalloproteinase 1