Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities.
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.
Delaissé
Jean-Marie
JM
Nordic Bioscience, Center for Clinical and Basic Research, DK-2730 Herlev, Denmark.
Andersen
Thomas L
TL
Engsig
Michael T
MT
Henriksen
Kim
K
Troen
Tine
T
Blavier
Laurence
L
D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D002465:Cell Movement; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010010:Osteoclasts / Q000201:enzymology* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology*
D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D020782:Matrix Metalloproteinases