TY - JOUR

T1 - Identification of the membrane-type matrix metalloproteinase MT1-MMP in osteoclasts

AU - Sato, Toyoko

AU - del Carmen Ovejero, M

AU - Hou, Peter Christian Asmussen

AU - Heegaard, Anne-Marie

AU - Kumegawa, M

AU - Foged, Niels

AU - Delaissé, Jean-Marie

PY - 1997

Y1 - 1997

N2 - The osteoclasts are the cells responsible for bone resorption. Matrix metalloproteinases (MMPs) appear crucial for this process. To identify possible MMP expression in osteoclasts, we amplified osteoclast cDNA fragments having homology with MMP genes, and used them as a probe to screen a rabbit osteoclast cDNA library. We obtained a cDNA of 1,972 bp encoding a polypeptide of 582 amino acids that showed more than 92% identity to human, mouse, and rat membrane-type 1 MMP (MT1-MMP), a cell surface proteinase believed to trigger cancer cell invasion. By northern blotting, MT1-MMP was found to be highly expressed in purified osteoclasts when compared with alveolar macrophages and bone stromal cells, as well as with various tissues. In situ hybridization on bone sections showed that MT1-MMP is expressed also in osteoclasts in vivo. Antibodies recognizing MT1-MMP reacted with specific plasma membrane areas corresponding to lamellipodia and podosomes involved, respectively, in migratory and attachment activities of the osteoclasts. These observations highlight how cells might bring MT1-MMP into contact with focal points of the extracellular matrix, and are compatible with a role of MT1-MMP in migratory and attachment activities of the osteoclast.

AB - The osteoclasts are the cells responsible for bone resorption. Matrix metalloproteinases (MMPs) appear crucial for this process. To identify possible MMP expression in osteoclasts, we amplified osteoclast cDNA fragments having homology with MMP genes, and used them as a probe to screen a rabbit osteoclast cDNA library. We obtained a cDNA of 1,972 bp encoding a polypeptide of 582 amino acids that showed more than 92% identity to human, mouse, and rat membrane-type 1 MMP (MT1-MMP), a cell surface proteinase believed to trigger cancer cell invasion. By northern blotting, MT1-MMP was found to be highly expressed in purified osteoclasts when compared with alveolar macrophages and bone stromal cells, as well as with various tissues. In situ hybridization on bone sections showed that MT1-MMP is expressed also in osteoclasts in vivo. Antibodies recognizing MT1-MMP reacted with specific plasma membrane areas corresponding to lamellipodia and podosomes involved, respectively, in migratory and attachment activities of the osteoclasts. These observations highlight how cells might bring MT1-MMP into contact with focal points of the extracellular matrix, and are compatible with a role of MT1-MMP in migratory and attachment activities of the osteoclast.

KW - Amino Acid Sequence

KW - Animals

KW - Base Sequence

KW - Blotting, Northern

KW - DNA, Complementary

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization

KW - Matrix Metalloproteinase 14

KW - Matrix Metalloproteinases, Membrane-Associated

KW - Metalloendopeptidases

KW - Molecular Sequence Data

KW - Osteoclasts

KW - Rabbits

KW - Sequence Homology, Amino Acid

M3 - Journal article

C2 - 9092941

VL - 110 ( Pt 5)

SP - 589

EP - 596

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

ER -