Journal
FEBS LETTERS
Volume 588, Issue 1, Pages 143-150Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2013.11.022
Keywords
HTRA1; Osteoclast; RANKL; Osteoblast; Crosstalk
Funding
- National Health and Medical Research Council of Australia
- Western Australia Medical & Health Research Infrastructure Fund
- UWA Research Development Award Scheme
- National Natural Science Foundation of China (NSFC) [81228013]
- Endeavour Research Fellowships
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Bone remodeling is regulated by secreted factors in the bone microenvironment. However, data regarding osteoclast-derived factors that influence osteoblast differentiation are lacking. Here, we show that HtrA1 is produced as a secreted protein during osteoclastogenesis, and negatively regulates osteoblast differentiation. Exogenous addition of recombinant HtrA1 attenuates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK1/2 and p38 phosphorylation in pre-osteoblasts. Our studies imply a unique mode of crosstalk in which HtrA1 is produced by both osteoclasts and osteoblasts and negatively regulates osteoblast differentiation, suggesting that HtrA1 may mediate the fine tuning of paracrine and autocrine regulations during bone remodeling processes. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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