The Runx2-stimulated transdifferentiation in skeletal primary myoblasts into an osteoblastic phenotype for bone tissue engineering, was investigated. The primary myoblasts were isolated from Balb/c mice and cultured in growth media. The microscopy and immunofluorescent staining exhibited reduced myotube fusion in Runx2-transduced myoblasts, which suggested inhibited myogenesis. The scaffolds seeded with Runx2-overexpressing myoblasts displayed regions of high X-ray attenuation by microCT and elevated elastic moduli by compression analysis at 42 days. The results show that the forced expression of Runx2 may bypass parallel BMP-2 stimulated regulatory pathways, leading to increased osteogenesis and mineralization.