Localization of cathepsins D, K, and L in degenerated human intervertebral discs.
METHODS
Localization of cathepsins D, K, and L in degenerated intervertebral discs was examined by immunohistochemistry.


OBJECTIVE
To determine the involvement of cathepsins in the pathomechanism of intervertebral disc degeneration by monitoring the immunolocalization of cathepsins in degenerated intervertebral disc tissue.


BACKGROUND
Cathepsins D, K, and L are enzymes that contribute to the matrix destruction seen in the articular cartilage affected by osteoarthritis and rheumatoid arthritis. However, little is known about the contribution of these cathepsins to intervertebral disc degeneration.


METHODS
Paraffin-embedded sections of degenerated intervertebral disc tissue collected at the time of surgery (13 discs from 12 patients) were immunohistochemically stained with antibodies for cathepsins D, K, and L. For further characterization of the stained cells, immunohistochemical detection of CD68 and TRAP staining were performed.


RESULTS
Hematoxylin and eosin staining revealed obvious signs of degeneration in all sections. Cathepsins D and L were immunolocalized in disc fibrochondrocytes at various sites exhibiting degeneration. Cathepsins K were found in tartrate-resistant acid phosphatase-positive multinucleated cells, in particular near the cleft within the cartilaginous endplate. However, few cells were positive for these cathepsins in anulus fibrosus that maintained the lamellar structure of collagen fibers.


CONCLUSIONS
Marked expression of cathepsins D and L was observed at the site of degeneration. Cathepsins D and K localized in tartrate-resistant acid phosphatase-positive multinucleated cells existed at the cleft between the cartilaginous endplate and vertebral body. The site-specific localization of these cathepsins suggests the association of these proteinases with endplate separation and disorganization of the anulus fibrosus in degenerative spinal disorders.
Ariga
K
K
Department of Orthopaedic Surgery, Osaka University Medical School, Suita, Osaka, Japan. ariga@ort.med.osaka-u.ac.jp
Yonenobu
K
K
Nakase
T
T
Kaneko
M
M
Okuda
S
S
Uchiyama
Y
Y
Yoshikawa
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002402:Cathepsin D / Q000378:metabolism*; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged
D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534130:CTSK protein, human; D056657:Cathepsin K; D002402:Cathepsin D