In addition to traditional approach for differentiation (biochemical factors), physical properties (elastic modulus) of the matrix will be becoming an important factor in differentiation of stem cells into different lineages. The porous scaffolds were prepared from the silk fibroin solutions 4%, 5%, 6%, 7% and 8.4% weight per volume (w/v) by freeze drying which produced scaffolds with the minimal changes in the pore size (96–160 μm) but with a ≈ 8-fold range of modulus (16 -131 kPa) in the wet condition. After isolation and characterization, stem cells of the apical papilla (SCAP) were seeded on the scaffolds and the osteogenic differentiation was evaluated by alizerin red staining, alkaline phosphatase test, real time PCR and immunohistochemistry. Results demonstrated modulus-dependent osteogenic differentiation of the apical papilla stem cells from 4% w/v (16 kPa) to 7% w/v (83 kPa) and then a sudden decrease of differentiation was observed in the 8.4% w/v (131 kPa). The highest differentiation was happened in the 7 % w/v (83 kPa). The stem cells can respond to elasticity ranged from 0.1 to 100 kPa and then differentiate into different lineages in terms of the amount of elastic modulus. This is probably the reason why bone differentiation potential of the SCAP decreases in the modulus over 100 kPa.