BMP9 expression patterns and bioactivity in oral cells and tissues: A scoping review

This scoping review aimed to compile and map the available evidence on bone morphogenetic protein 9 (BMP9) expression patterns and BMP9 bioactivity in oral cells and tissues.

Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, this comprehensive search was performed in six databases and gray literature, on November 26, 2024, with no restrictions. The eligibility criteria followed the PCC framework (Population: oral tissues/cells; Concept: BMP9; Context: studies that directly investigated BMP9 in oral or oral-related cells/tissues).

A total of 914 articles were identified, and 49 were selected for association between BMP9 and oral cells or tissues. Among studies that directly compared BMP9 and bone morphogenetic protein 2 (BMP2), BMP9 showed osteogenic or odontogenic bioactivity similar to or greater than that of BMP2. BMP9 consistently promoted osteogenic and odontogenic differentiation, mineralization, and bone regeneration, with context-dependent responses. Its bioactivity was mainly mediated by mitogen-activated protein kinase (MAPK) and Smad1/5/8 signaling, modulated by inflammatory microenvironments. In inflammatory settings, BMP9 effects were attenuated but could be partially restored through pathway modulation or combinatorial strategies.

Although the evidence remains preclinical and methodologically heterogeneous, BMP9 emerges as a highly potent osteoinductive factor in oral cells and tissues, with activity at low concentrations and relative resistance to classical antagonists. Its effects are context-dependent, influenced by inflammatory conditions and receptor availability. Standardized comparative studies and well-designed translational research are needed to establish its efficacy and safety.