Background: Recent reports have unveiled the potential of flavonoids to enhance bone
formation and assuage bone resorption due to their involvement in cell signaling pathways. They also
act as an effective alternative to circumvent the disadvantages associated with existing treatment
methods, which has increased their scope in orthopedic research. Valproic acid (VA, 2-propylpentanoic
acid) is one such flavonoid, obtained from an herbaceous plant, used in the treatment of
epilepsy and various types of seizures.
Objective: In this study, the role of VA in osteogenesis and the molecular mechanisms underpinning
its action in mouse mesenchymal stem cells (mMSCs) were determined.
Methods: Results: Cytotoxic studies validated VA’s amiable nature in mMSCs. Alizarin red and
von Kossa staining results showed an increased deposition of calcium phosphate in VA-treated
mMSCs, which confirmed the occurrence of osteoblast differentiation and mineralization at a cellular
level. At the molecular level, there were increased levels of expression of Runx2, a vital bone
transcription factor, and other major osteoblast differentiation marker genes in the VA-treated mMSCs.
Further, VA-treatment in mMSCs upregulated mir-21 and activated the mitogen-activated protein
kinase/extracellular signal-regulated kinase signaling pathway, which might be essential for
the expression/activity of Runx2.
Conclusion: Thus, the current study confirmed the osteoinductive nature of VA at the cellular and
molecular levels, opening the possibility for its application in bone therapeutics with mir-21.