Despite interesting in silico evidence, the specific role of mir-221 in osteogenesis has not been studied. We evaluated the osteogenic induction of transient-transfected anti-mir-221 in human unrestricted somatic stem cells and human mesenchymal stem cells both transcriptionally and translationally. In transfected unrestricted somatic stem cells, transcriptions of some osteogenic markers were twice that of the control and translations of osteopontin and osteocalcin were increased from 9 to 39 % and from 0 to 21 %, respectively. Up-regulation of transcribed osteogenic markers in transfected mesenchymal stem cells were 50 times greater than controls while no significant change in translations were observed. Prior to these analyses, the authenticity of stem cells, their osteogenic differentiation and transfection efficiency were verified. Transient modulation of mir-221 therefore suggests a mechanism for rapid induction of osteogenesis as a useful strategy for cell-based therapy.