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Repurpose dasatinib and quercetin: Targeting senescent cells ameliorates postmenopausal osteoporosis and rejuvenates bone regeneration

Ying Wang, Lingbin Che, Xi Chen, Zirui He, Dianwen Song, Yuan Yuan, Changsheng Liu

Bioactive Materials · 2023 · ▲ 76 citations

Cellular senescence Stem-cell exhaustion Chronic inflammation Stem-cell therapy Senolytics Rat Human

Abstract

Clinical therapies developed for estrogen-deficiency-driven postmenopausal osteoporosis (PMO) and related diseases, such as bone degeneration, show multiple adverse effects nowadays. Targeting senescent cells (SnCs) and the consequent senescence-associated secretory phenotype (SASP) with a combination of dasatinib and quercetin (DQ) is a recently developed novel therapy for multiple age-related diseases. Herein, we found that estrogen deficiency induced-bone loss was attributed to a pro-inflammatory microenvironment with SASP secretions and accelerated SnC accumulation, especially senescent mesenchymal stem cells (MSCs) characterized by exhaustion and dysfunction in middle aged rats. Systematically targeting SnCs with DQ strikingly ameliorated PMO and restored MSC function. Local administration of DQ and bone morphogenetic protein 2 (BMP2) in combination promoted osteogenic differentiation of MSCs and rejuvenated osteoporotic bone regeneration. Our results repurposed DQ as an attractive therapy for treating PMO and related diseases.

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Provenance

Source: OpenAlex
DOI: 10.1016/j.bioactmat.2023.01.009
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Fetched: 2026-06-07 MST

Cite this

APA

Wang, Y., Che, L., Chen, X., He, Z., Song, D., Yuan, Y., & Liu, C. (2023). Repurpose dasatinib and quercetin: Targeting senescent cells ameliorates postmenopausal osteoporosis and rejuvenates bone regeneration. <em>Bioactive Materials</em>. https://doi.org/10.1016/j.bioactmat.2023.01.009

Vancouver

Wang Y, Che L, Chen X, He Z, Song D, Yuan Y, et al. Repurpose dasatinib and quercetin: Targeting senescent cells ameliorates postmenopausal osteoporosis and rejuvenates bone regeneration. Bioactive Materials. 2023. doi:10.1016/j.bioactmat.2023.01.009.

BibTeX

@article{ying2023Repurp, title = {Repurpose dasatinib and quercetin: Targeting senescent cells ameliorates postmenopausal osteoporosis and rejuvenates bone regeneration}, author = {Ying Wang and Lingbin Che and Xi Chen and Zirui He and Dianwen Song and Yuan Yuan and Changsheng Liu}, journal = {Bioactive Materials}, year = {2023}, doi = {10.1016/j.bioactmat.2023.01.009}, }