Tuesday, November 3, 2009


MMP2 is upregulated by LSJL.  MMP2 is stimulated by GPC3 and GP3 knockout causes overgrowth.

Testican-1, an inhibitor of pro-MMP-2 activation, is expressed in cartilage.

"Testican-1 has been described to be an inhibitor of MT1-MMP and MT3-MMP mediated pro-MMP-2 activation. We studied the expression and localization of testican-1 in human articular cartilage.
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.
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.
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."

"Testican-1 is a highly conserved chimeric proteoglycan carrying both chondroitin sulfate and heparan sulfate chains, initially characterized as the precursor of a seminal plasma glycosaminoglycan-bearing peptide"

"testican-1 has been shown to inhibit the cysteine protease cathepsin L, and the heparan sulfate chains present on testican may contribute to the regulation of the collagenolytic activity of cathepsin K"

Testican1 was expressed most strongly in the proliferating zone.

"MMP-2 is an activator of pro-MMP-13"<-MMP13 may actually be beneficial for height growth when expressed in the hypertrophic zone.

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