USP7 Inhibition Promotes Early Osseointegration in Senile Osteoporotic Mice

Area of Science:

• Osteoimmunology
• Bone biology
• Regenerative medicine

Background:

• Elderly osteoporotic patients experience delayed osseointegration due to inflammation and impaired stem cell repair.
• Ubiquitin-specific peptidase 7 (USP7) regulates immune responses and stem cell differentiation.
• USP7 inhibition (P5091) shows potential for bone repair in osteoporosis.

Purpose of the Study:

• To investigate the roles of USP7 and P5091 in osteoimmunology and dental implant osseointegration in senile osteoporosis.
• To elucidate the mechanisms by which USP7 affects macrophages and mesenchymal stromal cells in aged osteoporotic bone.

Main Methods:

• USP7 depletion and P5091 treatment in senescent bone marrow-derived macrophages (BMDMs) and aged bone marrow mesenchymal stromal cells (BMSCs).
• mRNA sequencing (mRNA-Seq) to analyze molecular pathways.
• In vivo studies using senile osteoporotic mice to assess osseointegration around dental implants.

Main Results:

• USP7 inhibition reduced inflammation in senescent BMDMs and promoted osteogenic differentiation in aged BMSCs.
• USP7 depletion enhanced efferocytosis in senescent BMDMs via the EPSIN1/LRP1 pathway and induced selective apoptosis (senolysis) in aged BMSCs.
• P5091 treatment promoted early osseointegration in senile osteoporotic mice, linked to macrophage efferocytosis.

Conclusions:

• USP7 inhibition accelerates osseointegration in senile osteoporosis by enhancing macrophage efferocytosis and aged BMSC apoptosis.
• This study provides insights into peri-implant bone microenvironment interactions in osteoporosis.
• USP7 inhibition offers potential therapeutic strategies for improving dental implant outcomes in elderly osteoporotic patients.