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Integrin subunit β3 plays a crucial role in the movement of osteoclasts from the periosteum to the bone surface
Author(s) -
Holt Ian,
Marshall Michael J.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199804)175:1<1::aid-jcp1>3.0.co;2-s
Subject(s) - osteoclast , prostaglandin e2 , integrin , chemistry , periosteum , population , acid phosphatase , medicine , tartrate resistant acid phosphatase , endocrinology , microbiology and biotechnology , biology , anatomy , biochemistry , cell , enzyme , in vitro , environmental health
We have shown that, when mouse parietal bones were incubated in culture medium containing indomethacin, the number of tartrate‐resistant acid phosphatase‐positive osteoclasts (TRAP + OCs) on the bone surface was drastically reduced (down‐regulation), and the number on the periosteal membrane adjacent to the resorbing surface was increased. Subsequent incubation of bones with prostaglandin E2 (PGE2) rapidly reversed these changes (up‐regulation). In the work reported here, the osteoclast‐associated integrin subunit β3 was stained by immunohistochemistry. The β3‐positive osteoclast (β3 + OC) population on freshly isolated bone was comprised of about 67% TRAP + OCs and 33% TRAP − OCs. Like TRAP + OCs, β3 + OCs were reduced in number on the surface of bones incubated with indomethacin, but, in contrast to the TRAP + OCs, β3 + OCs were not seen on the periosteal membrane. Following up‐regulation of TRAP + OCs with PGE2, large numbers of β3 + OCs appeared on the bone surface and, again, were not seen on the periosteal membrane. Echistatin, a peptide that binds to the αvβ3 integrin on osteoclasts, was found to inhibit the up‐regulation of TRAP + OCs in a dose‐dependent manner but had no effect on the down‐regulation of TRAP + OCs. Similarly, echistatin inhibited the up‐regulation of β3 + OCs on the bone surface, and, under these conditions, β3 + OCs were observed on the periosteal membrane. The addition of anti‐β3 antibody also inhibited the up‐regulation of TRAP + OCs in response to PGE2. The association of β3 protein expression with the up‐regulated osteoclast and the inhibition of up‐regulation by echistatin and by anti‐β3 antibody provide strong evidence that β3 plays an essential role in the movement of osteoclasts from the membrane to the bone. J. Cell. Physiol. 175:1–9, 1998. © 1998 Wiley‐Liss, Inc.