Journal
BONE
Volume 117, Issue -, Pages 23-30Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2018.09.006
Keywords
Cathepsin K; Collagen type I; LAIR-1; Leukocyte receptor complex; NFATc1; Osteoclast
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Funding
- Canadian Institutes of Health Research [MOP-137091, PJT-152926]
- Reseau de recherche en sante buccodentaire et osseuse
- Faculty of Dentistry, McGill University
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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.
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