Collagen type I degradation fragments act through the collagen receptor LAIR-1 to provide a negative feedback for osteoclast formation

Research output: Contribution to journalArticle

Authors

  • Iris Boraschi-Diaz
  • John S. Mort
  • Dieter Brömme
  • Svetlana V. Komarova

Colleges, School and Institutes

External organisations

  • Faculty of Dentistry, McGill University
  • Shriners Hospital for Children-Canada
  • Faculty of Dentistry, University of British Columbia

Abstract

The major organic component of bone is collagen type I. Osteoclasts are terminally differentiated multinucleated cells of hematopoietic origin that are essential for physiological development of bone and teeth. We examined if osteoclast differentiation from murine bone marrow precursors is affected by collagen type I, or by its degradation products produced by human recombinant cathepsin K. Osteoclasts formation was dose-dependently inhibited in the presence of full length collagen type I or its 30–75 kDa degradation products added to the osteoclast differentiation media for the duration of an experiment. Collagen degradation fragments signaled through SH-2 phosphatases, inhibiting calcium signaling and NFATc1 translocation in osteoclast precursors. Osteoclasts and their precursors expressed a collagen receptor of leukocyte receptor complex family, LAIR-1. Importantly, collagen fragments failed to inhibit osteoclast formation from LAIR-1 deficient murine osteoclast precursors. This study demonstrates that collagen degradation fragments inhibit osteoclast formation acting through LAIR-1, providing a novel mechanism for the physiologically-relevant negative control of osteoclastogenesis.

Details

Original languageEnglish
Pages (from-to)23-30
Number of pages8
JournalBone
Volume117
Early online date12 Sep 2018
Publication statusPublished - 1 Dec 2018

Keywords

  • Cathepsin K, Collagen type I, LAIR-1, Leukocyte receptor complex, NFATc1, Osteoclast