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Inhibition of bone resorption in vitro by human enkephalinase (EC 3.4.24.11), a neutral metalloendopeptidase
Author(s) -
Ibbotson Kenneth J.,
D'souza Sharyn M.,
DeschodtLanckman Monique,
Appelboom Thierry E.
Publication year - 1992
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650070305
Subject(s) - enkephalinase , bone resorption , parathyroid hormone , chemistry , resorption , medicine , endocrinology , bone remodeling , proteolytic enzymes , biochemistry , enzyme , calcium , receptor , enkephalin , opioid
Bone metabolism is regulated by a wide variety of both circulating and locally produced peptides. The activity of such agents must be regulated, and one potential regulating mechanism is the inactivation of these peptides by locally produced proteolytic enzymes. One candidate for such a class of enzymes is enkephalinase (EC 2.3.24.11), a membrane‐bound neutral metalloendopeptidase that inhibits the activity of a range of biologically active peptides, including interleukin‐1 (IL‐1), a potent bone‐resorbing agent. In this study, we examined the effects of human enkephalinase on bone resorption in cultures of fetal rat long bones. We found that partially purified and highly purified enkephalinase inhibited bone resorption stimulated by parathyroid hormone (PTH) and IL‐1 α . The effects on PTH‐stimulated resorption were reversible, but enkephalinase did not inhibit prestimulated resorption. Enkephalinase also inhibited resorption induced by the nonpeptide stimulators 1,25‐(OH) 2 D 3 , retinoic acid, and prostaglandin E 2 (PGE 2 ). In addition, preliminary studies confirmed a previous report of the presence of an enkephalinase‐like activity in osteoblast‐like osteosarcoma cells. These data are consistent with the hypothesis that proteolytic enzymes, such as enkephalinase, may play a role in the local regulation of bone resorption.