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The Role of Senolytics in Osteoporosis
Erman Chen1,2,3,4, Jingjing Zhang5, Han Chen1,2,3,4
1Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310014, China.
Abstract:
Cellular senescence is a fundamental contributor to numerous dysfunctions and degenerative diseases, including osteoporosis. In genetically modified and preclinical animal models, therapeutic strategies targeting persistent senescent cells have been shown to delay and prevent osteoporosis. Senolytics are a class of drugs or compounds designed to selectively eliminate senescent cells without adversely affecting normal cells. In this review, we focus on the role of senolytic agents in regulating bone metabolism and their potential in the treatment of osteoporosis. We discussed major types of senolytics, such as natural compounds, kinase inhibitors, Bcl-2 family inhibitors, inhibitors of the mouse double minute 2/p53 interaction, heat shock protein 90 inhibitors, p53-binding inhibitors, and histone deacetylase inhibitors. This review also highlights the progress of senolytics in clinical trials. However, clinical results diverge from preclinical evidence. Therefore, senolytics should be critically evaluated as a potential therapeutic strategy for osteoporosis, with further validation required.
Insights
Senolytic drugs selectively eliminate senescent cells, showing promise for treating osteoporosis in preclinical studies. However, clinical trial results are mixed, requiring further validation for this senescent cell targeting therapy.
Area of Science:
- Gerontology
- Bone Biology
- Pharmacology
Background:
- Cellular senescence contributes to age-related diseases like osteoporosis.
- Targeting senescent cells with senolytics has shown potential in animal models for osteoporosis prevention and delay.
Purpose of the Study:
- To review the role of senolytic agents in bone metabolism.
- To evaluate the potential of senolytics for osteoporosis treatment.
Main Methods:
- Review of major senolytic drug classes including natural compounds, kinase inhibitors, and Bcl-2 family inhibitors.
- Analysis of senolytics targeting specific pathways like MDM2/p53 and HSP90.
- Examination of progress in clinical trials for senolytic therapies.
Main Results:
- Senolytics demonstrate potential in preclinical models for osteoporosis.
- Various senolytic drug classes target different cellular pathways.
- Clinical trial outcomes for senolytics in osteoporosis have shown divergence from preclinical findings.
Conclusions:
- Senolytics represent a potential therapeutic strategy for osteoporosis by targeting senescent cells.
- Critical evaluation and further validation are necessary due to discrepancies between preclinical and clinical results.
- Senolytic therapy requires careful assessment for effective osteoporosis treatment.
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