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Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-148491
  • 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 genesThe 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.show moreshow less

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Metadaten
Author: Regina Ebert, Peggy Benisch, Melanie Krug, Sabine Zeck, Jutta Meißner-Weigl, Andre Steinert, Martina Rauner, Lorenz Hofbauer, Franz Jakob
URN:urn:nbn:de:bvb:20-opus-148491
Document Type:Journal article
Faculties:Medizinische Fakultät / Lehrstuhl für Orthopädie
Language:English
Parent Title (English):Stem Cell Research
Year of Completion:2015
Volume:15
Pagenumber:231-239
Source:Stem Cell Research 15 (2015) 231–239. DOI: 10.1016/j.scr.2015.06.008
DOI:https://doi.org/10.1016/j.scr.2015.06.008
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:RT-PCR; WNT5A; expression; human atherosclerotic lesions; inflammation; lines; mesenchymal stem cells; mineralization; model; osteogenic differentiation; senescence; serum amyloid A; stromal cells; toll-like receptor
Release Date:2018/11/14
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International