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 SAA 1 (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) SAA 112 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.