In silico analysis to reveal underlying trans differentiation mechanism of Mesenchymal Stem Cells into Osteocytes

Background: Bone is a mineralized dynamic tissue, helps to protect and support the body. Osteoarthritis damages the cartilage and is responsible for the degeneration of the bone. Many cell-based therapies are available to repair the damage however, the non-availability of autologous cells and slows healing during regeneration of the damaged bone present major constraints. Hence, there is a need to search for a convenient and easily available cell source that can not only be used to repair the bone but can also enhance its regenerative potential. β-glycerophosphate, dexamethasone, and L-ascorbic-2-phosphate can differentiate mesenchymal stem cells (MSCs) into osteocytes. So far, the interaction of these compounds with osteocytes-specific proteins has not been studied. In this study, in silico analysis was performed to investigate the interaction of proteins with osteocytes specific compounds at the amino acids level.
Methods: 3D structures of Dexamethasone and L-ascorbic-2-phosphate (ascorbic acid) were drawn using Molecular Operating Environment (MOE). Then absorption, distribution, metabolism, and excretion (ADME) analysis was achieved using an online tool of “Swiss Package”. By Ramachandran plot, the predicted model of ALPL, MMP13, Osteonectin, and RunX2 proteins were evaluated. Then docking of these proteins with Dexamethasone and L-ascorbic-2-phosphate was performed.
Results: L-ascorbic-2-phosphate and Dexamethasone docked within the binding pockets of ALPL, RunX2, MMP13, and Osteonectin proteins, expressed in the bone cells. These compounds also showed good drug-likeness and pharmacokinetics properties.
Conclusion: It is concluded that β-glycerophosphate, dexamethasone, and L-ascorbic-2-phosphate are novel substrates for osteogenic differentiation. These compounds could increase the healing and regenerative potential of bone cells by enhancing the expression of osteocytes specific proteins.