ADP-ribosylation factor 1 regulates proliferation, migration, and fusion in early stage of osteoclast differentiation

Min Jae Kim, Hyunsoo Kim, Seoung Hoon Lee, Dong Ryun Gu, Soo Young Lee, Kyunghee Lee, Daewon Jeong

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7 Scopus citations


Small G-protein adenosine diphosphate (ADP)-ribosylation factors (ARFs) regulate a variety of cellular functions, including actin cytoskeleton remodeling, plasma membrane reorganization, and vesicular transport. Here, we propose the functional roles of ARF1 in multiple stages of osteoclast differentiation. ARF1 was upregulated during receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation and transiently activated in an initial stage of their differentiation. Differentiation of ARF1-deficient osteoclast precursors into mature osteoclasts temporarily increased in pre-maturation stage of osteoclasts followed by reduced formation of mature osteoclasts, indicating that ARF1 regulates the osteoclastogenic process. ARF1 deficiency resulted in reduced osteoclast precursor proliferation and migration as well as increasing cell-cell fusion. In addition, ARF1 silencing downregulated c-Jun N-terminal kinase (JNK), Akt, osteopontin, and macrophage colony-stimulating factor (M-CSF)-receptor c-Fms as well as upregulating several fusion-related genes including CD44, CD47, E-cadherin, and meltrin-a. Collectively, we showed that ARF1 stimulated proliferation and migration of osteoclast precursors while suppressing their fusion, suggesting that ARF1 may be a plausible inter-player that mediates the transition to osteoclast fusion at multiple steps during osteoclast differentiation.

Original languageEnglish
Pages (from-to)29305-29314
Number of pages10
JournalInternational Journal of Molecular Sciences
Issue number12
StatePublished - 9 Dec 2015

Bibliographical note

Publisher Copyright:
© 2015 by the authors; licensee MDPI, Basel, Switzerland.


  • ADP-ribosylation factor 1
  • Osteoclast differentiation
  • Osteoclast fusion


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