Testican-1, an inhibitor of pro-MMP-2 activation, is expressed in cartilage.
OBJECTIVE
Recently, testican-1 has been described to be an inhibitor of MT1-MMP and MT3-MMP mediated pro-MMP-2 activation. As MT1-MMP mediated pro-MMP-2 activation is of significance for cartilage destruction in osteoarthritis, we studied the expression and localization of testican-1 in human articular cartilage.


METHODS
Cartilage samples from the medial and lateral tibia plateau were obtained from osteoarthritic patients who underwent joint replacements, and were graded histomorphologically by Mankin score. Testican-1 expression was assessed in RNA isolated directly from cartilage as well as in freshly isolated chondrocytes by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantified by real-time RT-PCR. Testican-1 protein was localized by immunohistochemistry in human osteoarthritic cartilage samples, in human fetal knee joint, and in knees from mice.


RESULTS
Testican-1 mRNA could be detected in cartilage and in freshly isolated chondrocytes both from moderately and from severely damaged osteoarthritic cartilage. In the same donor, expression in chondrocytes from more severely affected regions was decreased compared with chondrocytes from less affected regions. By immunolocalization, testican-1 protein could be detected in chondrocytes predominantly of the superficial and transitional zones. Matrix staining in these zones was greatly reduced in samples from more severely affected osteoarthritic cartilage. A similar distribution was found in the articular cartilage of knees from 7-week-old mice. In addition to articular cartilage, testican-1 was also present in growth plate cartilage.


CONCLUSIONS
Testican-1 is a component of cartilage, both of the joint and of the growth plate. Given its activity as an inhibitor of MT1-MMP mediated pro-MMP-2 activation, it is reasonable to speculate that it participates in the regulation of matrix turnover in cartilage.
Hausser
Heinz-J
HJ
University of Ulm, Division for Biochemistry of Joint and Connective Tissue Diseases, Ulm, Germany. heinz-juergen.hausser@medizin.uni-ulm.de
Decking
Ralf
R
Brenner
Rolf E
RE
D000368:Aged; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000032:analysis; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007719:Knee Joint / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D000090023:Metallothionein 3; D051379:Mice; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D011509:Proteoglycans / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D011509:Proteoglycans; D012333:RNA, Messenger; C504369:SPOCK1 protein, human; C504370:Spock1 protein, mouse