MMP-13 is induced during chondrocyte hypertrophy

Abstract

During development, mRNA for matrix metalloproteinase-13 (MMP-13) is found associated with cartilage undergoing hypertrophy, suggesting that this collagenase plays a role in cell enlargement and/or cartilage calcification. Using chondrocytes from prehypertrophic cartilage of chick embryo sternae, we have examined the relationship between MMP-13 expression and the transition to hypertrophy. When hypertrophy was induced by serum-free culture with ascorbate and bone morphogenetic protein-2 (BMP-2), MMP-13 mRNA levels paralleled those for type X collagen. Chondrocytes from the caudal, nonhypertrophying portion of chick sternae expressed neither type X collagen nor MMP-13, confirming that MMP-13 mRNA is a marker for hypertrophy. Zymography with conditioned medium yielded a proteinase band at 59 kDa, which was absent in nonhypertrophic chondrocytes. A polyclonal antibody raised against chick MMP-13 reacted with the 59-kDa protein, confirming that it is MMP-13. Although mRNA for MMP-13 peaked at days 4-5 of culture, only low levels of MMP-13 activity were present, and the activity increased gradually in parallel with later increases in MMP-2. These results suggest that MMP-13 is activated by MMP-2 during chondrocyte maturation, and that the combination of both proteinases is required to prepare cartilage matrix for subsequent calcification, before endochondral ossification.

PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling

“…Other genes that have been shown to be upregulated during chondrocyte maturation include VEGF, MMP-13, and alkaline phosphatase [14,31,32]. Similar to the findings with colX, these other genes were dose-dependently inhibited by PGE2.…”

TGF-β2 is involved in the preservation of the chondrocyte phenotype under hypoxic conditions

“…Interestingly, we could only detect a non-significant trend toward upregulation of the core protein of key proteoglycan (PG) aggrecan (AGC1) after 48 h of low oxygen pressure. Of note, the key chondrocyte hypertrophy marker matrix metalloproteinase 13 (MMP13) (D'Angelo et al, 2000) showed a non-significant trend toward downregulation under these conditions. We further verified the expression of key chondrocyte phenotype markers, SOX9 and COL2, at protein level by Western blot analysis and confirmed a significant, more than 3-fold, upregulation of both (Fig.…”

Matrix metalloproteinase expression and function during fin regeneration in zebrafish: Analysis of MT1-MMP, MMP2 and TIMP2

“…To extend these studies, the current work has utilized zebrafish as an experimental model and has focused on the expression of a subset of MMPs (MT1-MMP and MMP-2) and a modulator of MMP activity (TIMP-2) during fin regeneration. These three molecules were selected because they can act 1) independently of one another (Nagase and Woessner, 1999) or 2) together as a unit during development (Strongin et al, 1995;Butler et al, 1998;D'Angelo et al, 2000). When functioning as a unit, they are involved in the activation of pro-MMP-2 to its active form (Strongin et al, 1995;Butler et al, 1998).…”