TY - JOUR
T1 - Serum amyloid a inhibits osteoclast differentiation to maintain macrophage function
AU - Kim, Jiseon
AU - Yang, Jihyun
AU - Park, Ok Jin
AU - Kang, Seok Seong
AU - Yun, Cheol Heui
AU - Han, Seung Hyun
N1 - Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2016/4
Y1 - 2016/4
N2 - 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.
AB - 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.
KW - C-Fos
KW - IFN regulatory factor 8
KW - NFATc1
KW - TLR
UR - http://www.scopus.com/inward/record.url?scp=84962459562&partnerID=8YFLogxK
U2 - 10.1189/jlb.3A0415-173R
DO - 10.1189/jlb.3A0415-173R
M3 - Article
C2 - 26538527
AN - SCOPUS:84962459562
SN - 0741-5400
VL - 99
SP - 595
EP - 603
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 4
ER -