Basic calcium phosphate crystals induce synthesis and secretion of 92 kDa gelatinase (gelatinase B/matrix metalloprotease 9) in human fibroblasts.
OBJECTIVE
Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe joint degeneration accompanied by synovial hypertrophy. The metalloprotease 92 kDa gelatinase (MMP-9) has been implicated in the degradation of extracellular matrix in osteoarthritis, but the ability of BCP crystals to induce gelatinase in human fibroblasts or in adult porcine chondrocytes has not previously been studied. The hypothesis that the mitogenic response to BCP crystals is accompanied by induction and secretion of MMP-9 was studied.


METHODS
MMP-9 messenger RNA (mRNA) was detected by northern blot and reverse transcription-polymerase chain reaction (RT-PCR). Gelatinase secretion was identified by western blot and zymography of conditioned media.


RESULTS
BCP crystals caused a concentration dependent induction of MMP-9 mRNA accumulation and protein secretion in human fibroblasts but not in adult porcine chondrocytes.


CONCLUSIONS
BCP crystals induce MMP-9 production by HF but not adult porcine chondrocytes. Fibroblast MMP-9 may be an important mediator of the joint destruction associated with synovial fluid BCP crystals.
McCarthy
G M
GM
Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
Macius
A M
AM
Christopherson
P A
PA
Ryan
L M
LM
Pourmotabbed
T
T
D000818:Animals; D015152:Blotting, Northern; D002130:Calcium Phosphates / Q000494:pharmacology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D020780:Matrix Metalloproteinase 9; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013268:Stimulation, Chemical; D013552:Swine
D002130:Calcium Phosphates; D012333:RNA, Messenger; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; C485829:calcium phosphate, dibasic, anhydrous