Expression of serum amyloid A transcripts in human bone tissues, differentiated osteoblast-like stem cells and human osteosarcoma cell lines.
Although the liver is the primary site of cytokine-mediated expression of acute-phase serum amyloid A (SAA) protein, extrahepatic production has also been reported. Besides its role in amyloidosis and lipid homeostasis during the acute-phase, SAA has recently been assumed to contribute to bone and cartilage destruction. However, expression of SAA in human osteogenic tissue has not been studied. Therefore, we first show that SAA1 (coding for the major SAA isoform) but not SAA2 transcripts are expressed in human trabecular and cortical bone fractions and bone marrow. Next, we show expression of (i) IL-1, IL-6, and TNF receptor transcripts; (ii) the human homolog of SAA-activating factor-1 (SAF-1, a transcription factor involved in cytokine-mediated induction of SAA genes); and (iii) SAA1/2 transcripts in non-differentiated and, to a higher extent, in osteoblast-like differentiated human mesenchymal stem cells. Third, we provide evidence that human osteoblast-like cells of tumor origin (MG-63 and SAOS-2) express SAF-1 under basal conditions. SAA1/2 transcripts are expressed under basal conditions (SAOS-2) and cytokine-mediated conditions (MG-63 and SAOS-2). RT-PCR, Western blot analysis, and immunofluorescence technique confirmed cytokine-mediated expression of SAA on RNA and protein level in osteosarcoma cell lines while SAA4, a protein of unknown function, is constitutively expressed in all osteogenic tissues investigated.
Kovacevic
Alenka
A
Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Center of Molecular Medicine, Graz, Austria.
Hammer
Astrid
A
Stadelmeyer
Elke
E
Windischhofer
Werner
W
Sundl
Monika
M
Ray
Alpana
A
Schweighofer
Natascha
N
Friedl
Gerald
G
Windhager
Reinhard
R
Sattler
Wolfgang
W
Malle
Ernst
E
D000210:Acute-Phase Reaction / Q000235:genetics / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014408:Biomarkers, Tumor; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha