L.B. contributed to this study when she worked with J.-M.D. at the ICP, Louvain University, Brussels, Belgium.
Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities
Article first published online: 18 JUL 2003
Copyright © 2003 Wiley-Liss, Inc.
Microscopy Research and Technique
Special Issue: Osteoclast Biology
Volume 61, Issue 6, pages 504–513, 15 August 2003
How to Cite
Delaissé, J.-M., Andersen, T. L., Engsig, M. T., Henriksen, K., Troen, T. and Blavier, L. (2003), Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities. Microsc. Res. Tech., 61: 504–513. doi: 10.1002/jemt.10374
- Issue published online: 18 JUL 2003
- Article first published online: 18 JUL 2003
- Manuscript Accepted: 23 OCT 2002
- Manuscript Received: 24 SEP 2002
- bone resorption;
- cell migration/recruitment;
- proteolytic signaling
The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute significantly to bone matrix solubilization in specific areas of the skeleton and in some developmental and pathological situations. Our discussion takes into account (1) the characteristics of the bone remodeling persisting in the absence of cathepsin K, (2) the ultrastructure of the resorption zone in response to inactivation of MMPs and of cathepsin K in different bone types, (3) bone resorption levels in MMP knockout mice compared to wild-type mice, (4) the identification of MMPs in osteoclasts and surrounding cells, and (5) the effect of different bone pathologies on the serum concentrations of specific collagen fragments believed to discriminate between cathepsin K and MMP cleavage. Next, we provide evidence that MMPs are very critical for osteoclast migration, thereby controlling also the cell-matrix interactions required for cell attachment/detachment. The evidence supporting this role is based on a model of osteoclast recruitment in primitive long bones, an assay of osteoclast invasion through collagen gel, and the effect of proteinase inhibitors/knockouts in these models. Furthermore, we mention observations indicating a role of MMPs in initiation of bone resorption. Finally, we emphasize the many distinct ways MMPs may alter focally the extracellular environment thereby regulating the osteoclast behavior. Although the understanding of MMPs in osteoclast biology is rapidly expanding, it is suspected that important roles remain to be discovered. Microsc. Res. Tech. 61:504–513, 2003. © 2003 Wiley-Liss, Inc.