Integrin subunit β3 plays a crucial role in the movement of osteoclasts from the periosteum to the bone surface
Autor: | Ian Holt, Michael J. Marshall |
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Rok vydání: | 1998 |
Předmět: |
medicine.medical_specialty
education.field_of_study Periosteum biology Physiology Chemistry Protein subunit Clinical Biochemistry Integrin Population Cell Biology stomatognathic diseases medicine.anatomical_structure Endocrinology stomatognathic system Biochemistry Downregulation and upregulation Osteoclast Internal medicine medicine biology.protein Immunohistochemistry Prostaglandin E2 education medicine.drug |
Zdroj: | Journal of Cellular Physiology. 175:1-9 |
ISSN: | 1097-4652 0021-9541 |
DOI: | 10.1002/(sici)1097-4652(199804)175:1<1::aid-jcp1>3.0.co;2-s |
Popis: | 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 beta3 was stained by immunohistochemistry. The beta3-positive osteoclast (beta3 + OC) population on freshly isolated bone was comprised of about 67% TRAP + OCs and 33% TRAP OCs. Like TRAP + OCs, beta3 + OCs were reduced in number on the surface of bones incubated with indomethacin, but, in contrast to the TRAP + OCs, beta3 + OCs were not seen on the periosteal membrane. Following up-regulation of TRAP + OCs with PGE2, large numbers of beta3 + OCs appeared on the bone surface and, again, were not seen on the periosteal membrane. Echistatin, a peptide that binds to the alphavbeta3 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 upregulation of beta3 + OCs on the bone surface, and, under these conditions, beta3 + OCs were observed on the periosteal membrane. The addition of anti-beta3 antibody also inhibited the up-regulation of TRAP + OCs in response to PGE2. The association of beta3 protein expression with the up-regulated osteoclast and the inhibition of up-regulation by echistatin and by anti-beta3 antibody provide strong evidence that beta3 plays an essential role in the movement of osteoclasts from the membrane to the bone. |
Databáze: | OpenAIRE |
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