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Title: Secretory clusterin inhibits osteoclastogenesis by attenuating M-CSF-dependent osteoclast precursor cell proliferation

Highlights: • We describe the expression and secretion of clusterin in osteoclasts. • Endogenous clusterin deficiency does not affect osteoclast formation. • Exogenous treatment with secretory clusterin decreases osteoclast differentiation. • Secretory clusterin attenuates osteoclast precursor cell proliferation by inhibiting M-CSF-mediated ERK activation. - Abstract: Secretory clusterin (sCLU)/apolipoprotein J is a multifunctional glycoprotein that is ubiquitously expressed in various tissues. Reduced sCLU in the joints of patients with bone erosive disease is associated with disease activity; however, its exact role has yet to be elucidated. Here, we report that CLU is expressed and secreted during osteoclastogenesis in mouse bone marrow-derived macrophages (BMMs) that are treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). CLU-deficient BMMs obtained from CLU{sup −/−} mice exhibited no significant alterations in OC differentiation in comparison with BMMs obtained from wild-type mice. In contrast, exogenous sCLU treatment significantly inhibited OC formation in both BMMs and OC precursor cultures. The inhibitory effect of sCLU was more prominent in BMMs than OC precursor cultures. Interestingly, treating BMMs with sCLU decreased the proliferative effects elicited by M-CSF and suppressed M-CSF-induced ERK activation of OC precursor cells without causing apoptotic cell death. This study providesmore » the first evidence that sCLU reduces OC formation by inhibiting the actions of M-CSF, thereby suggesting its protective role in bone erosion.« less
Authors:
;  [1] ;  [1] ;  [2] ;  [3] ; ; ;  [1] ;  [1] ;  [2] ;  [4] ;  [1] ;  [2]
  1. Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of)
  2. (Korea, Republic of)
  3. Department of Pharmacology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of)
  4. Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416619
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACID PHOSPHATASE; APOPTOSIS; BONE MARROW; CELL PROLIFERATION; DEOXYURIDINE; DISEASES; ENZYME IMMUNOASSAY; GLYCOPROTEINS; LIGANDS; MACROPHAGES; MICE; MOLYBDENUM CARBIDES; PATIENTS; RECEPTORS; SECRETION; SKELETON