P21′s Role In Ornj Pathogenesis: Bone Immune Microenvironment Mechanisms

Osteoradionecrosis of the jaws (ORNJ) is a severe complication following radiotherapy for head and neck tumors, this study aims to explore the molecular mechanisms of ORNJ and the regulatory role of the cell cycle regulator p21 in alterations of the bone immune microenvironment. This research identified radiation-induced p21-positive cell populations and their secretory phenotypes using 10-week-old male C57BL/6 mice ORNJ model and Single-cell RNA sequencing analysis of irradiated jaw bone tissue.In vitro experiments verified how radiation-induced p21 upregulation and subsequent inflammatory factor release disrupt bone immune microenvironment homeostasis. Single-cell RNA sequencing analysis revealed distinct p21-positive cell populations with characteristic inflammatory secretory phenotypes in irradiated jaw bone tissue of the ORNJ mouse model. Further characterization of these populations demonstrated their enrichment in pro-inflammatory cytokines and bone metabolism mediators. In vitro experiments confirmed that this radiation-induced p21-related inflammatory secretory phenotype directly disrupts bone homeostasis, thereby serving as a key initiating factor in the dysregulation of the jaw bone immune microenvironment. This discovery provides new molecular targets and theoretical foundations for the early diagnosis, intervention, and prevention strategies for ORNJ.