Mechanical loading is crucial for bone remodeling and osteoblast differentiation. FosB belongs to the AP-1 family of transcription factors, a group of proteins known to regulate osteoblast differentiation and bone formation. In mice, FosB is rapidly induced by mechanical stress at the transcriptional level. The aim of this study was to determine the effect of different mechanical stretch patterns on FosB gene expression and on osteogenic differentiation of human osteoblast precursor cells. Human bone-marrow-derived mesenchymal precursor cells were grown in flexible silicone dishes and stimulated by a daily application of three rounds of 2 h of cyclic stretch of either 2% or 8% elongation at 1 Hz on 3 consecutive days using a special motor-driven apparatus. By real-time PCR, we quantified FosB mRNA and the expression of genes involved in osteoblast differentiation such as Runx2 and collagen 1 to determine the osteogenic effect of mechanical stretch. Stretching induced FosB transcription and the expression of osteoblast markers in partly committed human mesenchymal precursor cells in a stretch- and time-dependent manner. We conclude that cyclic stretch-induced FosB expression and the upregulation of osteoblast genes plays a role in osteogenic differentiation of human mesenchymal precursor cells.