title: Afamin secreted from nonresorbing osteoclasts acts as a chemokine for preosteoblasts via the Akt-signaling pathway.
abstract: Although it is well known that osteoclastic bone resorption is followed by osteoblastic bone formation, questions remain as to when coupling factors are produced during bone resorption and which stages of bone formation are affected by these factors. To clarify these mechanisms, we established an in vitro system to investigate the coupling phenomenon. We obtained conditioned media (CM) from osteoclasts in the early and late stages of differentiation and from bone resorption stages. The collected CM was used to treat primary mouse calvarial osteoblasts and preosteoblastic MC3T3-E1 cells and to evaluate its influence on the migration, viability, proliferation, and differentiation of osteoblasts. We found that CM from osteoclasts in the early stage of differentiation predominantly stimulated the migration of osteoblastic lineages. By further performing fractional analyses of the CM with liquid chromatography-tandem mass spectrometry, we identified afamin, which has binding activity with vitamin E, as a possible coupling factor. The CM collected from afamin siRNA-transfected osteoclasts significantly suppressed preosteoblast migration. Afamin activated Akt in preosteoblasts, and pretreatment with Akt inhibitor significantly blocked afamin-stimulated preosteoblast migration. In conclusion, these results indicate that osteoclasts themselves play a central role in the coupling of bone resorption and formation by stimulating preosteoblast migration. In addition, we identified afamin as one of osteoclast-derived chemokines that affect preosteoblasts through the activation of the Akt-signaling pathway.
authors: Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, South Korea.
authors: Beom-Jun
authors: BJ
authors: Kim
authors: Young-Sun
authors: YS
authors: Lee
authors: Sun-Young
authors: SY
authors: Lee
authors: Sook-Young
authors: SY
authors: Park
authors: Hans
authors: H
authors: Dieplinger
authors: Sung Ho
authors: SH
authors: Ryu
authors: Kyungmoo
authors: K
authors: Yea
authors: Sunkyu
authors: S
authors: Choi
authors: Seung Hun
authors: SH
authors: Lee
authors: Jung-Min
authors: JM
authors: Koh
authors: Ghi Su
authors: GS
authors: Kim
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C576771:Afm protein, mouse; D000418:Albumins; D018925:Chemokines; D017077:Culture Media, Conditioned; D006023:Glycoproteins; D053245:RANK Ligand; D051057:Proto-Oncogene Proteins c-akt