The effects of inhibitors of cysteine-proteinases and collagenase on the resorptive activity of isolated osteoclasts.
The effects of specific inhibitors of cysteine-proteinases ((Z-Phe-Ala-CHN2: benzyloxycarbonyl-phenyl-alanyl alanyl diazomethane and E-64: trans-epoxy-succinyl-L-leucylamido(4-guanidino)-butane) and collagenase and collagenase ((Cl-1: N-(3-N-benzyloxycarbonyl amino-1-R-carboxypropyl)-L-leucyl-O-methyl-L-tyrosine N-methylamide) have been tested on the osteoclastic resorption of dentine. Chick osteoclasts were cultured in the presence or absence of 12.5 microM Z-Phe-Ala-CHN2, 40 or 60 microM E-64, or 40 or 100 microM Cl-1 for 1 or 2 days. In addition, osteoclasts were cultured on oyster shell calcitostracum with or without 12.5 microM Z-Phe-Ala-CHN2. Specimens were studied by light microscopy to count cells and resorption features and by scanning electron microscopy (SEM) stereophotogrammetry for the measurement of the depths, plan-areas and volumes of resorption pits. The numbers, depths and volumes (but not the plan-areas) of the resorption pits in dentine were significantly reduced by Z-Phe-Ala-CHN2 and E-64. Thus, for a given plan-area, the volumes and the depths of resorption pits were smaller in these experimental groups compared with control dentine specimens. The overall inhibition of resorption was at least 75%. Cl-1 did not have this inhibitory effect on the numbers or sizes of resorption pits in dentine. When the oyster calcitostracum was used as a substrate for the osteoclasts, Z-Phe-Ala-CHN2 did not reduce the numbers or volumes of pits, but increased the plan-areas and prevented the formation of deeper pits.(ABSTRACT TRUNCATED AT 250 WORDS)
Delaisse
J M
JM
International Institute of Cellular and Molecular Pathology, Universite Catholique de Louvain, Brussels, Belgium.
Boyde
A
A
Maconnachie
E
E
Ali
N N
NN
Sear
C H
CH
Eeckhout
Y
Y
Vaes
G
G
Jones
S J
SJ
D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D002642:Chick Embryo; D046508:Culture Techniques; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors; D003804:Dentin / Q000378:metabolism; D008297:Male; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010125:Ostreidae; D014907:Whales
D015853:Cysteine Proteinase Inhibitors; D003546:Cysteine Endopeptidases; D003012:Microbial Collagenase