BMP-2 Induced Signaling Pathways and Phenotypes: Comparisons Between Senescent and Non-senescent Bone Marrow Mesenchymal Stem Cells

The use of BMP-2 in orthopedic surgery is limited by uncertainty surrounding its effects on the differentiation of mesenchymal stem cells (MSCs) and how this is affected by cellular aging. This study compared the effects of recombinant human BMP-2 (rhBMP-2) on osteogenic and adipogenic differentiation between senescent and non-senescent MSCs. Senescent and non- senescent MSCs were cultured in osteogenic and adipogenic differentiation medium containing various concentrations of rhBMP-2. The phenotypes of these cells were compared by performing a calcium assay, adipogenesis assay, staining, real-time PCR, western blotting, and microarray analysis. rhBMP- 2 induced osteogenic differentiation to a lesser extent (P < 0.001 and P = 0.005 for alkaline phosphatase activity and -Ca2+ release) in senescent MSCs regardless of dose-dependent increase in both cells. However, the induction of adipogenic differentiation by rhBMP-2 was comparable between them. There was no difference between these two groups of cells in the adipogenesis assay (P = 0.279) and their expression levels of PPAR. were similar. Several genes such as CHRDL1, NOG, SMAD1, SMAD7, and FST encoding transcription factors were proposed to underlie the different responses of senescent and non-senescent MSCs to rhBMP-2 in microarray analyses. Furthermore, inflammatory, adipogenic, or cell death-related signaling pathways such as NF-kB or p38-MAPK pathways were upregulated by BMP-2 in senescent MSCs, whereas bone forming signaling pathways involving BMP, SMAD, and TGF-beta were upregulated in non-senescent MSCs as expected. This phenomenon explains bone forming dominance by non-senescent MSCs and possible frequent complications such as seroma, osteolysis, or neuritis in senescent MSCs during BMP-2 use in orthopedic surgery.

Automated summary

This study compared the effects of rhBMP-2 on osteogenic and adipogenic differentiation of senescent and non-senescent MSCs, with findings showing a lesser induction of osteogenic differentiation in senescent MSCs by rhBMP-2. The study also highlighted different gene expression and signaling pathways between the two groups of cells, with non-senescent MSCs showing dominance in bone forming pathways.