Interstitial collagenase activity stimulates the formation of actin rings and ruffled membranes in mouse marrow osteoclasts.
Interstitial collagenase activity stimulates bone resorption by mouse marrow osteoclasts [1]. Here, we show that collagenase activity promotes bone resorption by activating adherent osteoclasts to resorb bone. Inhibition of interstitial collagenase activity, either with peptidomimetic hydroxymates or with a specific anti-interstitial collagenase inhibiting antibody, reduced bone resorption by 73-92%. Equal numbers of osteoclasts adhered to bone in the presence of collagenase inhibitors and osteoclast survival was unaffected. In contrast, formation of actin rings and polarization of the vacuolar-H+-ATPase (V-ATPase) to ruffled membranes, two indicators of osteoclast activation, were decreased by inhibiting collagenase activity and stimulated in the presence of cleaved or heat-denatured type I collagen in proportion to increases and decreases of bone resorptive activity. Addition of excess recombinant osteoprotegerin-ligand to cultures did not restore bone resorption in the presence of interstitial collagenase inhibitors. These data support the hypothesis that cleaved collagen stimulates osteoclastic bone resorption by triggering cytoskeletal reorganization and transport of V-ATPase from cytoplasmic stores to ruffled membranes.
Holliday
L S
LS
Department of Orthodontics, University of Florida College of Dentistry, Gainesville, FL 32610, USA. sholliday@dental.ufl.edu
Welgus
H G
HG
Hanna
J
J
Lee
B S
BS
Lu
M
M
Jeffrey
J J
JJ
Gluck
S L
SL
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001854:Bone Marrow Cells; D001862:Bone Resorption; D002352:Carrier Proteins / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003804:Dentin / Q000187:drug effects; D008264:Macrophages; D020781:Matrix Metalloproteinase 1 / Q000276:immunology / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
D000199:Actins; D019138:Antibodies, Blocking; D002352:Carrier Proteins; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D011480:Protease Inhibitors; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D020781:Matrix Metalloproteinase 1; D025262:Vacuolar Proton-Translocating ATPases