ABSTRACT
Remodeling and relaxation of the mouse pubic symphysis (PS) are central events in parturition. The involvement of endogenous proteins such as matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), and cathepsins in these phenomena remains unclear. In this work, we used a combination of immunolocalization, protein expression/activity, and relative messenger RNA (mRNA) expression to examine the changes in selected MMPs (-2, -9, and -8), TIMPs (-1 and -2), and cathepsins (B and K) during pregnancy and postpartum in mice. Immunohistochemistry revealed the presence of all of these proteins in the cytoplasm of chondrocytes, fibrochondrocytes, and fibroblast-like cells in the interpubic tissues. Zymography showed increases in the active forms of MMP-2 and -9 primarily on days 15 to 19 of pregnancy. Western blotting showed enhanced expression of MMP-8 on days 12 to 15 of pregnancy, with no changes in cathepsins B and K. Matrix metalloproteinases 2, TIMP-1 and -2, and cathepsin B had significant relative gene expression throughout pregnancy. These findings indicate that during pregnancy and postpartum there are variations in the expression and activity of proteins that may have an important role in remodeling the pubic symphysis during these events.
Subject(s)
Cathepsins/metabolism , Matrix Metalloproteinases/metabolism , Postpartum Period/metabolism , Pregnancy, Animal/metabolism , Pubic Symphysis/metabolism , Tissue Inhibitor of Metalloproteinases/metabolism , Animals , Cathepsins/genetics , DNA/chemistry , DNA/genetics , Female , Matrix Metalloproteinases/genetics , Mice , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Polymerase Chain Reaction , Pregnancy , Pubic Symphysis/enzymology , Pubic Symphysis/ultrastructure , Tissue Inhibitor of Metalloproteinases/geneticsABSTRACT
A specific local erosion of the medial edges of the pubic bones is induced by administration of estradiol cyclopentylpropionate (ECP) to thyroparathyroidectomized mice. This paper presents both histochemical and biochemical evidence that porcine thyrocalcitonin (TCT) inhibits this estrogen-mediated resorption of the pubic symphysis. A marked increase in osteoclasts with a resultant increase in demonstrable sites of acid phosphatase (AcP) activity was observed in serial sections of resorbing pubic symphyses from ECP-treated animals. Bioassay of excised pubic symphyses revealed a concomitant increase in AcP activity. When mice were treated with TCT in combination with ECP, a marked decrease in osteoclasts with a resultant decrease in demonstrable sites of AcP activity and inhibition of the resorption process occurred. The mouse pubic symphysis thus appears to offer a model for exploring cellular mechanisms by which TCT regulates bone metabolism.
