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Updated: Aug 20, 2026

Sequential In vivo Imaging of Osteogenic Stem/Progenitor Cells During Fracture Repair
Published on: May 23, 2014
p21 Inhibition Rescues Radiation-Induced Osteogenic Dysfunction and Promotes Bone Regeneration in Osteoradionecrosis
Jiaying Shi1, Shuxian Lin1, Jiayu Yan1
1Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, China.
Background:
Osteoradionecrosis of the jaw (ORNJ) is a severe radiotherapy complication with unclear molecular drivers. CDKN1A/p21 is upregulated by radiation-induced DNA damage, but its role in ORNJ remains unknown.
Methods:
An ORNJ mouse model was established. Single-cell RNA-sequencing of irradiated mandibles was analyzed and validated in vivo. Irradiated jaw bone marrow mesenchymal stem cells (JBMMSCs) were characterized. p21 was inhibited using UC2288 and siRNA. A UC2288-loaded AlgMA hydrogel was developed for local delivery.
Results:
Bone healing was compromised in ORNJ. Radiation induced p21 upregulation in osteogenic lineage cells, which promoted Rb dephosphorylation and aberrant Smad2/3 phosphorylation, thereby suppressing Runx2-mediated osteogenesis. p21 inhibition reversed this cascade and restored osteogenic differentiation. Local delivery of UC2288@AlgMA significantly enhanced bone regeneration.
Conclusion:
p21-related signaling impairs bone healing after irradiation, and local UC2288 delivery via AlgMA hydrogels represents a viable strategy to enhance ORNJ regeneration.
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