Serum amyloid a inhibits osteoclast differentiation to maintain macrophage function

Jiseon Kim, Jihyun Yang, Ok Jin Park, Seok Seong Kang, Cheol Heui Yun, Seung Hyun Han

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Serum amyloid A is an acute phase protein that is elevated under inflammatory conditions. Additionally, the serum levels of serum amyloid A are associated with the progression of inflammatory arthritis; thus, serum amyloid A might be involved in the regulation of osteoclast differentiation. In the present study, we examined the effects of serumamyloid A on osteoclast differentiation and function. When bone marrow-derived macrophages, as osteoclast precursors, were stimulated with serum amyloid A in the presence of M-CSF and receptor activator of nuclear factor-kB ligand, osteoclast differentiation and its boneresorption activity were substantially inhibited. TLR2 was important in the inhibitory effect of serum amyloid A on osteoclast differentiation, because serum amyloid A stimulated TLR2. The inhibitory effect was absent in bone marrow-derived macrophages obtained from TLR2- deficient mice. Furthermore, serum amyloid A inhibited the expression of c-Fos and nuclear factor of activated T cells c1, which are crucial transcription factors for osteoclast differentiation, but prevented downregulation of IFN regulatory factor-8, a negative regulator of osteoclast differentiation. In contrast, serumamyloid A sustained the endocytic capacity of bone marrow-derived macrophages and their ability to induce the proinflammatory cytokines, IL-6, IL-1b, and TNF-a. Taken together, these results suggest that serum amyloid A, when increased by inflammatory conditions, inhibits differentiation of macrophages to osteoclasts, likely to maintain macrophage function for host defense.

Original languageEnglish
Pages (from-to)595-603
Number of pages9
JournalJournal of Leukocyte Biology
Volume99
Issue number4
DOIs
StatePublished - Apr 2016

Keywords

  • C-Fos
  • IFN regulatory factor 8
  • NFATc1
  • TLR

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