TY  - JOUR
A1  - Ebert, Regina
A1  - Benisch, Peggy
A1  - Krug, Melanie
A1  - Zeck, Sabine
A1  - Meißner-Weigl, Jutta
A1  - Steinert, Andre
A1  - Rauner, Martina
A1  - Hofbauer, Lorenz
A1  - Jakob, Franz
T1  - Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells
JF  - Stem Cell Research
N2  - The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation andmineralization. In vitro aged hMSC developed a senescence-associated secretory phenotype (SASP), resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1\(\beta\), CXCL1, CXCL2) expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1) induced SASP-related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP-like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis.
KW  - human atherosclerotic lesions
KW  - senescence
KW  - expression
KW  - toll-like receptor
KW  - mineralization
KW  - osteogenic differentiation
KW  - serum amyloid A
KW  - inflammation
KW  - mesenchymal stem cells
KW  - WNT5A
KW  - model
KW  - lines
KW  - stromal cells
KW  - RT-PCR
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148491
VL  - 15
ER  -