Epigenetic modifications play a crucial role in regulating stem cell differentiation. Among these, N6-methyladenosine (m⁶A) modification significantly impacts mRNA stability and translation. However, its role in dental stem cell differentiation remains largely unexplored. Functional assays, including ALP activity, alizarin red S staining, qPCR, and Western blot, were conducted to assess odontogenic differentiation. Then, an in vivo dentin formation model was used to validate our findings. Additionally, we employed RNA stability assays and m⁶A site mutagenesis to investigate the regulatory mechanism of m⁶A modification in GATA2-mediated differentiation. Our results demonstrated that overexpression of GATA2 significantly promoted SCAP odontogenic differentiation. Moreover, in vivo studies confirmed that GATA2 overexpression enhances dentin formation in mouse models. Conversely, knockdown of GATA2 or mutation of its m⁶A sites led to reduced mRNA stability and decreased odontogenic differentiation. m⁶A modification is enriched in the 3′ untranslated region (3′UTR) of GATA2 mRNA, regulating its stability and expression. Our findings indicate that m⁶A modification contributes to the post-transcriptional regulation of GATA2, enhancing its stability and promoting SCAP-mediated odontogenic differentiation and dentin formation. This study provides new insights into the epigenetic regulation of dental stem cells and suggests a potential molecular target for dental tissue regeneration.

Bisphosphonates (BPs) are cornerstone therapeutic agents for the management of metabolic bone disorders and skeletal complications associated with malignant tumors. However, their long-term administration is accompanied by the risk of developing bisphosphonate-related osteonecrosis of the jaw (BRONJ). In recent years, the pathogenesis of BRONJ has remained a major focus at the intersection of osteoimmunology and oral medicine. This review systematically summarizes the latest advances in the understanding of BRONJ pathogenesis, including the direct disruption of osteoclast differentiation and bone remodeling coupling by bisphosphonates, the systemic reprogramming of immune cell subsets and inflammatory signaling pathways, the multifaceted suppression of angiogenesis and the endothelial–stromal–immune axis, and the toxic impairment of oral soft tissue repair capacity. Building upon these mechanistic insights, we further discuss the modifying and synergistic effects of local oral risk factors, microbial dysbiosis, systemic comorbidities, and genetic susceptibility on the initiation and progression of BRONJ. Furthermore, emerging therapeutic strategies targeting these pathogenic mechanisms are highlighted, including restoration of small GTPase prenylation through modulation of metabolic pathways, reconstruction of T-cell subset homeostasis via immunomodulatory approaches, enhancement of local vascularization through pro-angiogenic interventions, and preservation of soft tissue barrier integrity. Collectively, this review provides a comprehensive and multidimensional overview of the pathological landscape of BRONJ and offers a theoretical framework for clinical risk stratification and the development of personalized prevention and treatment strategies.