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

作　　者：Ying Wang Lingbin Che Xi Chen Zirui He Dianwen Song Yuan Yuan Changsheng Liu 

机构地区：[1]Key Laboratory for Ultrafine Materials of Ministry of Education,Frontiers Science Center for Materiobiology and Dynamic Chemistry,Engineering Research Center for Biomaterials of Ministry of Education,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai,200237,PR China [2]Department of Orthopedics,Shanghai General Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,200080,China

出　　处：《Bioactive Materials》2023年第7期13-28,共16页生物活性材料（英文）

基　　金：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)。

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 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.

关 键 词：Postmenopausal osteoporosis Dasatinib and quercetin Senescent cells Mesenchymal stem cell Bone regeneration 

分 类 号：R318[医药卫生—生物医学工程]