Osteogenic differentiation and inflammatory response of recombinant human bone morphogenetic protein-2 in human...

The aim of the present study was to investigate the osteogenic potential of human maxillary sinus membrane (hMSM)-derived cells, and the role of recombinant human bone morphogenetic protein-2 (rhBMP-2) in the inflammatory response of hMSM-derived cells and gingival fibroblasts following sinus floor elevation procedure (SFE). hMSM-derived cells from the samples were isolated, subcultured, and analyzed using immunohistochemical staining and flow cytometry. The hMSM-derived cells obtained from passage 6 were used for Alizarin Red staining and quantitative reverse transcription-quantitative PCR to observe its osteogenic activity and inflammatory reaction upon supplementation with rhBMP-2. The hMSM-derived cells were shown to be heterogeneous, as indicated by their positive expression of human mesenchymal stem cell markers (STRO-1, high mobility group AT-hook 2, CD44, CD105 and OCT-3/4), fibroblast cell marker (fibroblast-specific protein 1) and epithelial cell marker (epithelial cell adhesion molecule). Calcium nodules were found to be more notably evident in the rhBMP-2 group, following osteogenic differentiation. The gene expression of osteogenic markers was significantly upregulated in the cells supplemented with rhBMP-2. Supplementation with rhBMP-2 also enhanced the expression of inflammatory markers in hMSM-derived cells and gingival fibroblasts; however, NF-κB and TNF-α expression was not significantly increased compared with the control in the hMSM-derived cells. hMSM contains mesenchymal stem cells (MSCs) capable of differentiating into osteogenic cells. The supplementation of rhBMP-2 enhanced osteogenic differentiation and induced an inflammatory response which was greater in gingival fibroblasts compared with hMSM-derived cells. In summary, the hMSM is a potential contributor to the osteogenic process following SFE, and the use of rhBMP-2 may increase the inflammatory response accordingly. The gingival tissue may be responsible for the increased inflammatory response by rhBMP-2 and postoperative complications.