Stem cell-homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model

被引：188

作者：

Zhu, Jinjin ^{[1
,2
,3
]}

Yang, Shuhui ^{[3
]}

Qi, Yadong ^{[4
]}

Gong, Zhe ^{[1
,2
]}

Zhang, Haitao ^{[1
,2
]}

Liang, Kaiyu ^{[1
,2
]}

Shen, Panyang ^{[1
,2
]}

Huang, Yin-Yuan ^{[3
]}

Zhang, Zhe ^{[3
]}

Ye, Weilong ^{[3
]}

Yue, Lei ^{[4
]}

Fan, Shunwu ^{[1
,2
]}

Shen, Shuying ^{[1
,2
]}

Mikos, Antonios G. ^{[5
]}

Wang, Xiumei ^{[3
]}

Fang, Xiangqian ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Orthoped Surg, Sch Med, Hangzhou 310016, Peoples R China

[2] Key Lab Musculoskeletal Syst Degenerat & Regenera, Hangzhou 310016, Peoples R China

[3] Tsinghua Univ, Sch Mat Sci & Engn, State Key Lab New Ceram & Fine Proc, Key Lab Adv Mat,Minist Educ, Beijing 100084, Peoples R China

[4] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Gastroenterol, Hangzhou 310016, Zhejiang, Peoples R China

[5] Rice Univ, Dept Bioengn, 6100 Main St, Houston, TX 77005 USA

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 13期

基金：

国家重点研发计划;

关键词：

ARTICULAR-CARTILAGE; MIRNA DELIVERY; SILENCING RNA; IN-VIVO; KNEE; REPAIR; IDENTIFICATION; MICROFRACTURE; PROLIFERATION; MICRORNAS;

D O I：

10.1126/sciadv.abk0011

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose a hydrogel-based miRNA delivery strategy to rejuvenate impaired cartilage by creating a regenerative microenvironment to mitigate chondrocyte senescence that mainly contributes to cartilage breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found to be markedly down-regulated in OA cartilage, and their up-regulation suppressed the expression of matrix metalloproteinases and senescence-associated genes (P16(INK4a)/P21) via ten-eleven-translocation enzyme 1 (TET1). An injectable bioactive self-assembling peptide nanofiber hydrogel was applied to deliver agomir- 29b-5p, which was functionalized by conjugating a stem cell-homing peptide SKPPGTSS for endogenous synovial stem cell recruitment simultaneously. Sustained miR-29b-5p delivery and recruitment of synovial stem cells and their subsequent differentiation into chondrocytes led to successful cartilage repair and chondrocyte rejuvenation. This strategy enables miRNA-based therapeutic modality to become a viable alternative for surgery in OA treatment.

引用

页数：16

共 71 条

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