TY - JOUR
T1 - A scrutiny of matrix metalloproteinases in osteoclasts
T2 - evidence for heterogeneity and for the presence of MMPs synthesized by other cells
AU - Andersen, Thomas L
AU - del Carmen Ovejero, Maria
AU - Kirkegaard, Tove
AU - Lenhard, Thomas
AU - Foged, Niels T
AU - Delaissé, Jean-Marie
PY - 2004/11
Y1 - 2004/11
N2 - Genetic diseases and knockout mice stress the importance of matrix metalloproteinases (MMPs) in skeletal turnover. Our study aims at clarifying which MMPs are expressed by osteoclasts. Previous analyses of this basic question led to conflicting reports in the literature. In the present study, we used a variety of approaches: PCR, Northern blots, Slot blots, in situ hybridization, and immunohistochemistry. We analyzed osteoclasts in culture as well as osteoclasts in native bone at different locations and compared mouse and rabbit osteoclasts. Osteoclasts express MMP-9 and -14 in all conditions, although to a variable extent, and they are able to synthesize MMP-3, -10, and -12, at least under some circumstances. The induction of a given MMP in osteoclasts is influenced by its environment (e.g., osteoclast culture vs. native bone, and various sites within the same bone) and depends on the species (e.g., mouse vs. rabbit). Osteoclasts show high amounts of MMP-2 and -13 protein presumably made to a large extent by other cells, thereby documenting how proteinases of nonosteoclastic origin may contribute to osteoclast activities and giving insight in why the resorptive activity of purified osteoclasts appears insensitive to MMP inhibitors. Our study shows that the confusion about osteoclastic MMPs in the literature reflects the remarkable ability of osteoclasts to adapt to their environment, as required by the structural or functional diversity of bone tissue. Our observations provide basic information needed for understanding the emerging role of MMPs in controlling cell signaling and bone resorption.
AB - Genetic diseases and knockout mice stress the importance of matrix metalloproteinases (MMPs) in skeletal turnover. Our study aims at clarifying which MMPs are expressed by osteoclasts. Previous analyses of this basic question led to conflicting reports in the literature. In the present study, we used a variety of approaches: PCR, Northern blots, Slot blots, in situ hybridization, and immunohistochemistry. We analyzed osteoclasts in culture as well as osteoclasts in native bone at different locations and compared mouse and rabbit osteoclasts. Osteoclasts express MMP-9 and -14 in all conditions, although to a variable extent, and they are able to synthesize MMP-3, -10, and -12, at least under some circumstances. The induction of a given MMP in osteoclasts is influenced by its environment (e.g., osteoclast culture vs. native bone, and various sites within the same bone) and depends on the species (e.g., mouse vs. rabbit). Osteoclasts show high amounts of MMP-2 and -13 protein presumably made to a large extent by other cells, thereby documenting how proteinases of nonosteoclastic origin may contribute to osteoclast activities and giving insight in why the resorptive activity of purified osteoclasts appears insensitive to MMP inhibitors. Our study shows that the confusion about osteoclastic MMPs in the literature reflects the remarkable ability of osteoclasts to adapt to their environment, as required by the structural or functional diversity of bone tissue. Our observations provide basic information needed for understanding the emerging role of MMPs in controlling cell signaling and bone resorption.
KW - Animals
KW - Blotting, Northern
KW - Blotting, Western
KW - Bone Resorption/enzymology
KW - Cells, Cultured
KW - Collagenases/genetics
KW - Gene Expression/genetics
KW - In Situ Hybridization
KW - Matrix Metalloproteinase 10
KW - Matrix Metalloproteinase 13
KW - Matrix Metalloproteinase 2/genetics
KW - Matrix Metalloproteinase 9/genetics
KW - Matrix Metalloproteinases/genetics
KW - Metalloendopeptidases/genetics
KW - Metatarsal Bones/cytology
KW - Mice
KW - Osteoclasts/enzymology
KW - Protein Transport
KW - Rabbits
KW - Rats
KW - Skull/cytology
KW - Tibia/cytology
U2 - 10.1016/j.bone.2004.06.019
DO - 10.1016/j.bone.2004.06.019
M3 - Article
C2 - 15542036
SN - 8756-3282
VL - 35
SP - 1107
EP - 1119
JO - Bone
JF - Bone
IS - 5
ER -