Transcriptomic Profiling of Mesenchymal Stromal Cells Derived From Medication‐Related Osteonecrosis of the Jaw

OBJECTIVE: Medication-related osteonecrosis of the jaw is a severe adverse effect of antiresorptive agents. Although autologous mesenchymal stromal cell therapy is a potential treatment, the effects of medication-related osteonecrosis of the jaw microenvironment on mesenchymal stromal cells remain unclear. METHODS: Mesenchymal stromal cells were isolated from medication-related osteonecrotic jaw lesions of five patients and healthy gingival tissue. Proliferation and differentiation capacities were assessed; transcriptomic profiles were analysed using bulk RNA sequencing. RESULTS: Mesenchymal stromal cells derived from medication-related osteonecrosis of the jaw exhibited proliferation and differentiation capacities comparable to those of gingiva-derived mesenchymal stromal cells. However, substantial transcriptomic alterations in 1336 genes (444 upregulated, 892 downregulated) were identified. Downregulated genes were primarily associated with RNA splicing and processing, including SF3B1 and RBM39. Upregulated genes were enriched in translation, immune responses, and proteoglycan metabolism, including POSTN and FN1, suggesting chronic exposure to medications associated with medication-related osteonecrosis of the jaw induces transcriptomic alterations consistent with disease-associated reprogramming of mesenchymal stromal cells, compromising their regenerative capacity. CONCLUSIONS: This study provides insights into the applicability and limitations of using mesenchymal stromal cells from patients with medication-related osteonecrosis of the jaw and identifies potential molecular targets for future cell-based regenerative strategies.