ArticleJournal of dental research2025
USP7 Inhibition Promotes Early Osseointegration in Senile Osteoporotic Mice.
Article in Journal of dental research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Therapy-Induced Senescence (TIS) and SASP: The p53-Mediated Interplay in Cancer Progression and Treatment.International journal of molecular sciences · 2025Review
- Unraveling the meta-hallmarks between senescent and tumor cells: A new perspective for senolytic drug discovery.Acta pharmaceutica Sinica. B · 2025Review
- The Role of Senolytics in Osteoporosis.Biomolecules · 2025Review
- Association between bone mineral density T-score and respiratory sarcopenia in older adults.Frontiers in medicine · 2025Article
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Authors and funding
11 authors.
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Abstract
Although elderly osteoporotic patients have similar implant survival rates compared with those of normal individuals, they require longer healing periods to achieve proper osseointegration. This may be related to chronic inflammatory responses and impaired stem cell repair functions in the osteoporotic bone microenvironment. Recently, the deubiquitinating enzyme, ubiquitin-specific peptidase 7 (USP7), was found to regulate the macrophage immune response and modulate stem cell osteogenic differentiation. The selective inhibitor of USP7, P5091, has also been found to promote bone repair and homeostasis in osteoporotic conditions. However, the roles of USP7 and P5091 in osteoimmunology and dental implant osseointegration under senile osteoporotic conditions remain unclear. In this study, USP7 depletion and P5091 were shown to inhibit inflammation in senescent bone marrow-derived macrophages (BMDMs) and promote osteogenic differentiation in aged bone marrow mesenchymal stromal cells (BMSCs). Furthermore, mRNA-Seq revealed that USP7 depletion could enhance efferocytosis in senescent BMDMs through the EPSIN1/low-density lipoprotein receptor-related protein 1 (LRP1) pathway and selectively induce apoptosis (senolysis) in aged BMSCs. In senile osteoporotic mice, we found that the osseointegration period was prolonged compared with young mice, and P5091 promoted the early stage of osseointegration, which may be related to macrophage efferocytosis around the implant. Collectively, this study suggests that USP7 inhibition may accelerate the osseointegration process in senile osteoporotic conditions by promoting macrophage efferocytosis and aged BMSCs apoptosis. This has implications for understanding the cellular interactions and signaling mechanisms in the peri-implant bone microenvironment under osteoporotic conditions. It may also provide clinical significance in developing new therapies to enhance osseointegration quality and shorten the edentulous period in elderly osteoporotic patients.
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