Calcification of articular cartilage in human osteoarthritis.
OBJECTIVE
Hypertrophic chondrocyte differentiation is a key step in endochondral ossification that produces basic calcium phosphates (BCPs). Although chondrocyte hypertrophy has been associated with osteoarthritis (OA), chondrocalcinosis has been considered an irregular event and linked mainly to calcium pyrophosphate dihydrate (CPPD) deposition. The aim of this study was to determine the prevalence and composition of calcium crystals in human OA and analyze their relationship to disease severity and markers of chondrocyte hypertrophy.


METHODS
One hundred twenty patients with end-stage OA undergoing total knee replacement were prospectively evaluated. Cartilage calcification was studied by conventional x-ray radiography, digital-contact radiography (DCR), field-emission scanning electron microscopy (FE-SEM), and synovial fluid analysis. Cartilage calcification findings were correlated with scores of knee function as well as histologic changes and chondrocyte hypertrophy as analyzed in vitro.


RESULTS
DCR revealed mineralization in all cartilage specimens. Its extent correlated significantly with the Hospital for Special Surgery knee score but not with age. FE-SEM analysis showed that BCPs, rather than CPPD, were the prominent minerals. On histologic analysis, it was observed that mineralization correlated with the expression of type X collagen, a marker of chondrocyte hypertrophy. Moreover, there was a strong correlation between the extent of mineralization in vivo and the ability of chondrocytes to produce BCPs in vitro. The induction of hypertrophy in healthy human chondrocytes resulted in a prominent mineralization of the extracellular matrix.


CONCLUSIONS
These results indicate that mineralization of articular cartilage by BCP is an indissociable process of OA and does not characterize a specific subset of the disease, which has important consequences in the development of therapeutic strategies for patients with OA.
Fuerst
M
M
Department of Orthopaedic Surgery, University Medical Center Hamburg-Eppendorf, Clinic Bad Bramstedt, Martinistrasse 52, Hamburg, Germany. mfuerst@uke.uni-hamburg.de
Bertrand
J
J
Lammers
L
L
Dreier
R
R
Echtermeyer
F
F
Nitschke
Y
Y
Rutsch
F
F
Schäfer
F K W
FK
Niggemeyer
O
O
Steinhagen
J
J
Lohmann
C H
CH
Pap
T
T
Rüther
W
W
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D002114:Calcinosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002130:Calcium Phosphates / Q000378:metabolism; D002358:Cartilage, Articular / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D024121:Collagen Type X / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D010003:Osteoarthritis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D011856:Radiographic Image Enhancement; D012720:Severity of Illness Index
D002130:Calcium Phosphates; D024121:Collagen Type X