Unveiling the Therapeutic Potential of hUCMSC-Derived EVs in Intervertebral Disc Degeneration through <i>MALAT1</i>/<i>miR-138-5p</i>/SLC7A11 Coexpression Regulation
Xiaojun Yu, Xiaofan Bai, Yun-Kun Qu, Shanxi Wang, Jianwei Zhang, Wenlong Yang, Sibo Wang, Yuli Yang, Yingguang Wang, Ding-Jun Hao, Yuan-Ting Zhao
Abstract
Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.