Proliferation and differentiation of osteoblasts by many transcription factors, including transcription factors from the family of Helix-Loop-Helix proteins, Zinc Finger proteins, Lucine Zipper proteins, and Runt domain-containing proteins. Also, proto-oncogenes such as C-myc, C-jun and C-fos are controlled and regulated. Two transcription factors specific to the osteoblastic lineage include RUNX2 and OSTERIX (SP7). These transcription factors transcribe osteoblast-specific genes including osteocalcin, osteopontin, collagen type IαI and bone sialoprotein. Other transcription factors involved in osteoblastic differentiation include TWIST1, ZBTB16, DLX5, MSX2, FRA1, DLX3, ATF4, and C/EBP. The role of methylation changes in the promoter region of most of these genes as well as their expression pattern in the osteoblastic differentiation of mesenchymal stem cells has been identified and indicates the changes in the methylation pattern of the promoter region of specific genes of the osteoblast lineage during the osteoblastic differentiation of mesenchymal stem cells. At the same time, the information that shows the changes of methylation of the whole genome during osteoblastic differentiation of mesenchymal stem cells can provide complementary information in this field. Zoledronic acid is an amino bisphosphonate and a strong inhibitor of bone resorption and at the same time an activator of osteoblasts in bone formation. This drug is used to prevent skeletal accidents in patients with advanced bone malignancies and also in the treatment of some bone disorders associated with increased bone turnover, such as Paget's disease and osteoporosis. The main mechanism of this drug is to inhibit osteoclasts and thus inhibit calcium reabsorption from bones, but at the same time, this drug increases the number and activity of osteoblasts by accelerating the osteoblastic differentiation of mesenchymal stem cells, whose molecular mechanism is still not well known. Epigenetic mechanisms, especially DNA methylation, play an important role in the differentiation process.