文献类型：期刊文献

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

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

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Minist Educ, Engn Res Ctr Biomed Mat, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai 200237, Peoples R China;[4]Fudan Univ, Eye & ENT Hosp, Dept Otolaryngol, Shanghai 200031, Peoples R China

年份：2026

卷号：60

起止页码：163

外文期刊名：BIOACTIVE MATERIALS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001691296400001)】；

基金：This research was 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 Materiobiology and Dynamic Chemistry (JKVD1211002). We thank the staff members of the Integrated Laser Microscopy System (https://cstr.cn/31129.02.NFPS.CLMIS) at the National Facility for Protein Science in Shanghai (https://cstr.cn/31129.02.NFPS), for providing technical support and assistance in data collection and analysis.

语种：英文

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

摘要：Excessive glucocorticoid (GC) administration is a major contributor to bone marrow senescence, which subsequently 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 prostaglandin/PPAR gamma/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.