Role of plants and phytochemicals in promoting proliferation and osteogenic differentiation of dental mesenchymal stem cells: a comprehensive review

Abstract

Abstract Objectives Dental mesenchymal stem cells (MSCs) represent a promising source for regenerative medicine due to their accessibility and capacity to differentiate into osteoblasts and other lineages. Osteogenic differentiation of dental MSCs is essential for bone formation and is regulated by multiple signaling pathways, cytokines, growth factors, and transcription factors. This review aims to summarize the effects of plant-derived extracts and phytochemicals on the proliferation and osteogenic differentiation of dental MSCs. Methods In this review, an extensive literature search was conducted covering studies from the past 10 years, using different online databases (SCOPUS, Google Scholar, PubMed, Web of Science, Science Direct). The following keywords related to plants, phytochemical compounds, dental MSCs proliferation, osteogenic differentiation, stem cells, periodontal ligament stem cells, osteogenic markers expression, and key signaling pathways. Results Numerous plant extracts and isolated phytochemicals, including flavonoids, phenolic acids, terpenoids, polysaccharides, and alkaloids, enhanced dental MSC proliferation, alkaline phosphatase activity, mineralization, and expression of osteogenic markers. These effects were primarily mediated through modulation of key bone-related signaling pathways such as Wnt/β-catenin, BMP/Smad, PI3K/Akt, and ERK/MAPK, alongside anti-inflammatory and antioxidant actions. Several compounds demonstrated superior biocompatibility relative to conventional agents. Conclusion Plant-derived compounds may provide safer and more effective options to enhance the osteogenic differentiation of dental MSCs and could serve as alternatives or complements to conventional osteogenic agents, supporting the need for further preclinical and clinical studies. Graphical abstract