Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression

Qiang Zhang; Le Cao; Shanqi Zou; Yuanling Feng; Xudong Miao; Lu Huang; Yongping Wu

doi:10.1155/2022/1157498

Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MicroRNA-181c-5p Promote BMP2-Induced Repair of Cartilage Injury through Inhibition of SMAD7 Expression

Stem Cells Int. 2022 Jun 24:2022:1157498. doi: 10.1155/2022/1157498. eCollection 2022.

Authors

Qiang Zhang¹, Le Cao¹, Shanqi Zou², Yuanling Feng³, Xudong Miao¹, Lu Huang¹, Yongping Wu¹

Affiliations

¹ Foot and Ankle Group of Orthopaedics, The Second Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou 310000, China.
² Obstetrics Department, The Second Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou 310000, China.
³ Foot and Ankle Group of Orthopaedics, The Second Hospital of Quzhou, Quzhou 324000, China.

Abstract

The therapy role of mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) in cartilage regeneration has been well studied. Herein, we tried to analyze the role of human umbilical cord MSC- (hUCMSC-) EVs carrying microRNA- (miR-) 181c-5p in repair of cartilage injury. After successful isolation of hUCMSCs, the multidirectional differentiation abilities were analyzed. Then, the EVs were isolated and identified. After coculture of PKH26-labled EVs with bone marrow MSCs (BMSCs), the biological behaviors of which were detected. The relationship between the predicted early posttraumatic osteoarthritis-associated miRNA, miR-181c-5p, and SMAD7 was verified. Gain- and loss-of functions were performed for investing the role of miR-181c-5p and SMAD7 in BMP-induced chondrogenesis in vitro and in vivo. hUCMSC-EVs could be internalized by BMSCs and promote the proliferative, migratory, and chondrogenic differentiation potentials of BMSCs. Additionally, miR-181c-5p could target and inhibit SMAD7 expression to promote the bone morphogenic protein 2- (BMP2-) induced proliferative, migratory, and chondrogenic differentiation potentials of BMSCs. Also, overexpression of SMAD7 inhibited the repairing effect of BMP2, and overexpression of BMP2 and miR-181c-5p further promoted the repair of cartilage injury in vivo. Our present study highlighted the repairing effect of hUCMSC-EVs carrying miR-181c-5p on cartilage injury.