Matrix metalloproteinases (
MMPs) are
endopeptidases that degrade the
proteins of the extracellular matrix (ECM). Expression and activity of the
MMPs are essential for embryogenesis, where
MMPs participate in the normal ECM remodeling that occurs during tissue morphogenesis and development. Studies have demonstrated that
MMP gene expression is inhibited by
glucocorticoids in mammalian cell culture systems and that exposure to
glucocorticoids causes developmental abnormalities in several species. Therefore, we proposed that
glucocorticoids impede normal development through alteration of
MMP expression. Zebra fish (Danio rerio) were used as a model to study MMP-13 expression both during normal embryogenesis and following acute exposure to two
glucocorticoids,
dexamethasone, and
hydrocortisone. MMP-13 is one of three
collagenases identified in vertebrates that catalyzes the degradation of type I
collagens at neutral pH. MMP-13 expression varied during zebra fish development, with peak expression at 48 h post-fertilization (hpf).
Morpholino knockdown studies showed that MMP-13 expression is necessary for normal zebra fish embryogenesis. Acute exposure to
dexamethasone and
hydrocortisone resulted in abnormal zebra fish development including
craniofacial abnormalities, altered somitogenesis, blood pooling and pericardial and yolk sac
edema as well as increased MMP-13
mRNA and activity at 72 hpf. In situ hybridization experiments were used to confirm the increase in MMP-13 expression following
glucocorticoid treatment and showed elevated MMP-13 expression in the rostral trunk, brain, eye, heart, and anterior kidney of treated embryos. These data demonstrate that normal zebra fish embryogenesis requires MMP-13 and that
dexamethasone and
hydrocortisone modulate the expression of this gene, leading to increased activity and potentially contributing to subsequent dysmorphogenesis.