The polymine spermine regulates osteogenic differentiation in adipose stem cells.
For bone tissue engineering, it is important that mesenchymal stem cells (MSCs) differentiate into osteoblasts. To develop a method for differentiation of adipose tissue-derived mesenchymal stem cells (AT-MSCs) along the osteogenic lineage, we studied the effect of polyamines, which are organic cations implicated in bone growth and development, on differentiation of AT-MSCs. Treatment of goat-derived AT-MSCs with 1,25-dihydroxyvitamin-D3 (1,25(OH)(2)D(3)), which stimulates osteogenic differentiation, for 7 days induced gene expression of the polyamine-modulated transcription factor-1 (PMF-1) and spermidine/spermine N (1)-acetyltransferase (SSAT), which are both involved in polyamine metabolism, suggesting that polyamines are involved in osteogenic differentiation of AT-MSCs. Furthermore, treatment of AT-MSCs with the polyamine spermine-regulated gene expression of runx-2, a transcription factor involved in early stages of osteogenic differentiation, and that of osteopontin, a bone matrix protein expressed in later stages of osteogenic differentiation. Runx-2 gene expression was increased 4 and 14 days after a short 30 min. treatment with spermine, while osteopontin gene expression was only increased 4 days after spermine treatment. Finally, alkaline phosphatase activity, which is intimately involved in the formation of extracellular matrix of bone, was increased 4 weeks after the 30 min.-spermine treatment of AT-MSCs. In conclusion, this study shows for the first time that the polyamine spermine regulates differentiation of AT-MSCs along the osteogenic lineage, which can be used as a new method for differentiation of AT-MSCs along the osteogenic lineage. Therefore, polyamines may constitute a promising tool for bone tissue engineering approaches using AT-MSCs, such as a one-step surgical procedure for spinal interbody fusion.
Tjabringa
G S
GS
Department of Oral Cell Biology, Academic Center of Dentistry Amsterdam (ACTA), Universiteit van Amsterdam and Vrije Universiteit, Research Institute MOVE, Amsterdam, The Netherlands.
Zandieh-Doulabi
B
B
Helder
M N
MN
Knippenberg
M
M
Wuisman
P I J M
PI
Klein-Nulend
J
J
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006041:Goats; D010012:Osteogenesis / Q000187:drug effects*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D050659:Core Binding Factor Alpha 1 Subunit; D053495:Osteopontin; D013096:Spermine; D000099228:Diamine N-Acetyltransferase