文献类型：期刊文献

中文题名：Sulfated polysaccharide prevents senescent adipocyte-driven osteonecrosis by stem cell fate reprogramming

作者：Shuang Zhang[1,2];Shunshu Deng[1,3];Kai Dai[2,3];Yang Liu[4];Jing Wang[1,2,3];Changsheng Liu[2,3]

机构：[1]The State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai,200237,PR China;[2]Engineering Research Center for Biomedical Materials of the Ministry of Education,East China University of Science and Technology,Shanghai,200237,PR China;[3]Frontiers Science Center for Materiobiology and Dynamic Chemistry,East China University of Science and Technology,Shanghai,200237,PR China;[4]Department of Otolaryngology,Eye&ENT Hospital,Fudan University,Shanghai,200031,PR China

年份：2026

卷号：60

期号：6

起止页码：163

中文期刊名：Bioactive Materials

外文期刊名：生物活性材料(英文)

基金：supported by the Basic Science Center Program of National Natural Science Foundation of China(No.T2288102);the Key Program of the National Natural Science Foundation of China(No.32230059);the Foundation of Frontiers Science Center for Materiobi-ology and Dynamic Chemistry(JKVD1211002).

语种：英文

中文关键词：Osteonecrosis;Sulfated polysaccharide;Aging;Adipocyte;Glucocorticoid

摘要：Excessive glucocorticoid(GC)administration is a major contributor to bone marrow senescence,which subse-quently contributes to the development of osteonecrosis.Conventional therapeutic approaches have shown limited efficacy,largely because current interventions are typically initiated only after a definitive diagnosis of bone deterioration-by which time the disease has often progressed to an intermediate or advanced stage,thereby missing the optimal therapeutic window for effective intervention.Here,we report that a semi-synthetic sulfated chitosan(SCS)can effectively prevent the onset of GC-induced osteonecrosis by suppressing complete senescence of the bone marrow and maintaining coupling between arterial vascularization and osteogenesis.SCS attenuates the spread of GC-induced primary adipocyte senescence into secondary senescence,effectively limiting the progressive amplification of the senescence cascade.Rather than directly intervening in the pros-taglandin/PPARγ/INK positive feedback loop within the senescent adipocyte lineage,SCS functions as an extracellular matrix component that activates the IGF-1/PI3K/Akt/mTOR signaling cascade.This activation reprograms the GC-induced lineage commitment bias of bone marrow leptin receptor^(+)(LepR^(+))mesenchymal stem cells(MSCs),leading to the downregulation of adipogenic differentiation and lipid biosynthesis pathways.By attenuating upstream senescence-driving cues at the source,SCS effectively suppresses the initiation and propagation of bone marrow adipocyte senescence.Thus,this highly bioactive polysaccharide halts the onset of senescence-driven osteonecrosis at an early stage,offering a promising avenue toward upstream,preventive interventions for skeletal aging and degeneration.