title: Secretory clusterin inhibits osteoclastogenesis by attenuating M-CSF-dependent osteoclast precursor cell proliferation.
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(-/-) 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 provides the first evidence that sCLU reduces OC formation by inhibiting the actions of M-CSF, thereby suggesting its protective role in bone erosion.
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Bongkun
authors.initials: B
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Soon-Suk
authors.initials: SS
authors.lastname: Kang
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea; Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
authors.forename: Bon-Hong
authors.initials: BH
authors.lastname: Min
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Da-Hyun
authors.initials: DH
authors.lastname: Song
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea; Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Youngsup
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea; Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea. Electronic address: ejchang@amc.seoul.kr.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D051152:Clusterin / Q000378:metabolism*; D008262:Macrophage Activation / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: C495243:Clu protein, mouse; D051152:Clusterin; D016173:Macrophage Colony-Stimulating Factor
keywords: Clusterin; Differentiation; ERK; Osteoclast; Proliferation