Reducing polyamine levels favors osteogenic differentiation of MSCs 

Snyder-Robinson Syndrome (SRS) is a rare disorder that is characterized by severe osteoporosis. SRS is caused by a mutation in the gene coding for Spermine Synthase (SMS). SMS converts spermidine into spermine via an electrophilic addition. Therefore, SRS patients show increased spermidine/spermine ratios, as compared to healthy individuals. Much still needs to be elucidated about the role of polyamines during osteogenesis. Using human bone marrow-derived Multipotent Stromal Cells (MSCs) undergoing osteogenic differentiation, we found that supplementation with spermidine inhibits differentiation. Even more, during osteogenic differentiation we found that the polyamine catabolic enzyme Spermidine/Spermine Acetyltransferase (SAT1) is strongly upregulated, further suggesting that polyamine depletion is necessary for osteogenesis. In line with these findings, inhibition of polyamine synthesis directly promotes osteogenesis. Therefore, our results in vitro suggest that reduction of polyamines is necessary for osteogenic differentiation.