Title
Erosive arthritis in a patient with pycnodysostosis: An experiment of nature
Author
Ainola, M.
Valleala, H.
Nykänen, P.
Risteli, J.
Hanemaaijer, R.
Konttinen, Y.T.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
Objective. The excellent poster painter Henri de Toulouse-Lautrec is the most famous patient with cathepsin K-deficient pycnodysostosis. Cathepsin K is believed to play a major role in osteoclast-driven bone resorption. In this study we explored the role of cathepsin K in bone resorption in a patient with a cathepsin K mutation causing pycnodysostosis in whom psoriatic arthritis also developed. We hypothesized that the patient would develop only inflammatory synovitis but would not develop bone erosions or other osteolytic changes. Methods. Monocytes from the patient with pycnodysostosis and normal control monocytes were isolated and stimulated to fuse and form multinuclear osteoclast-like cells, which were identified by evaluating messenger RNA expression of osteoclast markers. The ability to resorb bone was assessed by determining the extent of pit formation and levels of collagen degradation products generated by cathepsin K (C-terminal crosslinking telopeptide of type I collagen [CTX]) and matrix metalloproteinases (pyridinoline crosslinked C-terminal telopeptide of type I collagen). These experiments were also done in normal control cells after incubation with the cathepsin K inhibitor E64 during bone resorption. Results. In contrast to our a priori hypothesis, the patient developed a mutilating disease with extensive bony erosions associated with lysis of some of the distal phalanges of her hands and feet. After stimulation of monocytes from this patient, the cells formed multinuclear tartrate-resistant acid phosphatase-positive and calcitonin receptor-positive multikaryons, which, however, totally lacked cathepsin K. These multinuclear cells were able to resorb bone but, in contrast to normal control osteoclasts, did not produce CTX. The resorption pattern was abnormal in that, unlike normal control osteoclasts, both osteoclasts from the patient and E64-inhibited osteoclasts did not leave extensive osteoclast trails, but were relatively sessile. Conclusion. In this "experiment of nature" we observed that cathepsin K is not necessary for bone degradation. These findings may be pertinent to our understanding of the functions of cathepsin K inhibitors, which are currently being developed as drugs to treat metabolic bone diseases. © 2008, American College of Rheumatology.
Subject
Health
acid phosphatase tartrate resistant isoenzyme
calcitonin receptor
carboxy terminal telopeptide
cathepsin K
folic acid
hydroxychloroquine
ketoprofen
matrix metalloproteinase
messenger RNA
methotrexate
n [n (3 carboxyoxirane 2 carbonyl)leucyl]agmatine
prednisolone
salazosulfapyridine
adult
article
bone defect
bone erosion
case report
collagen degradation
controlled study
drug withdrawal
dysostosis
female
hand radiography
human
human cell
monocyte
multinuclear cell
nucleotide sequence
osteoclast
osteolysis
priority journal
psoriatic arthritis
pyknodysostosis
rash
synovitis
Acid Phosphatase
Arthritis, Psoriatic
Bone Resorption
Cathepsins
Cells, Cultured
Dysostoses
Female
Humans
Middle Aged
Monocytes
Osteoclasts
Receptors, Calcitonin
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http://resolver.tudelft.nl/uuid:8547e859-1323-4d71-8f5b-153657f80afb
DOI
https://doi.org/10.1002/art.23996
TNO identifier
241079
ISSN
0004-3591
Source
Arthritis and Rheumatism, 58 (11), 3394-3401
Document type
article