文献类型：期刊文献

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

作者：Wang, Ying[1];Che, Lingbin[2];Chen, Xi[1];He, Zirui[1];Song, Dianwen[2];Yuan, Yuan[1];Liu, Changsheng[1]

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Key Lab Ultrafine Mat, Sch Mat Sci & Engn,Minist Educ,Engn Res Ctr Biomat, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Orthoped, Sch Med, Shanghai 200080, Peoples R China

年份：2023

卷号：25

起止页码：13

外文期刊名：BIOACTIVE MATERIALS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000935571100001)】；

基金：This work is supported from:Frontiers Science Center for Materiobiology and Dynamic Chemistry (No. JKVD1211002)Natural Science Foundation of China for Innovative Research Groups (No.51621002)National Natural Science Foundation of China (Nos. 81571828, 31971264, 32101151)Basic Science Center Project of National Natural Science Foundation of China (T2288102)

语种：英文

外文关键词：Postmenopausal osteoporosis; Dasatinib and quercetin; Senescent cells; Mesenchymal stem cell; Bone regeneration

摘要：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 se-cretions 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.