Afamin secreted from nonresorbing osteoclasts acts as a chemokine for preosteoblasts via the Akt-signaling pathway

Beom Jun Kim, Young Sun Lee, Sun Young Lee, Sook Young Park, Hans Dieplinger, Sung Ho Ryu, Kyungmoo Yea, Sunkyu Choi, Seung Hun Lee, Jung Min Koh, Ghi Su Kim

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)431-440
Number of pages10
JournalBone
Volume51
Issue number3
DOIs
Publication statusPublished - 1 Sep 2012

    Fingerprint

Keywords

  • Afamin
  • Chemokine
  • Coupling
  • Osteoblast

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Kim, B. J., Lee, Y. S., Lee, S. Y., Park, S. Y., Dieplinger, H., Ryu, S. H., Yea, K., Choi, S., Lee, S. H., Koh, J. M., & Kim, G. S. (2012). Afamin secreted from nonresorbing osteoclasts acts as a chemokine for preosteoblasts via the Akt-signaling pathway. Bone, 51(3), 431-440. https://doi.org/10.1016/j.bone.2012.06.015