Characterization of chondrocyte alkaline phosphatase as a potential mediator in the dissolution of calcium pyrophosphate dihydrate crystals.
OBJECTIVE
To characterize chondrocyte alkaline phosphatase (ALP) distribution and expression in cartilage and monolayer cultures.


METHODS
Sections of bovine articular cartilage or chondrocyte monolayer cultures were stained for ALP activity. Surface ALP was released with bacterial phosphatidylinositol specific phospholipase C (PI-PLC). The levels of ALP mRNA were determined by Northern blot analysis using a cDNA probe to bovine ALP.


RESULTS
Chondrocyte ALP activity dissolves calcium pyrophosphate dihydrate (CPPD) crystals. About 5% of the total chondrocytes contained ALP activity. The ALP positive cells were present only in the deep layers of articular cartilage adjacent to the subchondral bone. Thirty to forty percent of the total ALP activity was present on the chondrocyte surface and was released by PI-PLC. Both chondrocyte ALP activity and mRNA levels decreased with time in culture. However, continuous dexamethasone treatment stimulated the expression of ALP in ALP positive chondrocytes, sufficiently to replace all of the chondrocyte surface ALP released following PI-PLC treatment.


CONCLUSIONS
Since ALP hydrolyzes pyrophosphate and dissolves CPPD crystals, our data suggest that regulation of chondrocyte ALP activity and expression in cartilage may prove useful for the development of a specific therapy CPPD arthropathy.
Xu
Y
Y
Department of Pathology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Canada.
Pritzker
K P
KP
Cruz
T F
TF
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002131:Calcium Pyrophosphate / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology*; D002417:Cattle; D003907:Dexamethasone / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism
D012333:RNA, Messenger; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D002131:Calcium Pyrophosphate