Vascular Smooth Muscle Cells Transdifferentiate into Chondrocyte-Like Cells and Facilitate Meniscal Fibrocartilage Regeneration

Wenqiang Yan; Jin Cheng; Haoda Wu; Zeyuan Gao; Zong Li; Chenxi Cao; Qingyang Meng; Yue Wu; Shuang Ren; Fengyuan Zhao; Hongde Wang; Ping Liu; Jianquan Wang; Xiaoqing Hu; Yingfang Ao

doi:10.34133/research.0555

Vascular Smooth Muscle Cells Transdifferentiate into Chondrocyte-Like Cells and Facilitate Meniscal Fibrocartilage Regeneration

Research (Wash D C). 2024 Dec 23:7:0555. doi: 10.34133/research.0555. eCollection 2024.

Authors

Wenqiang Yan^{1

2

3}, Jin Cheng^{1

2

3}, Haoda Wu^{1

2

3}, Zeyuan Gao^{1

2

3}, Zong Li^{1

2

3}, Chenxi Cao^{1

2

3}, Qingyang Meng^{1

2

3}, Yue Wu^{1

2

3}, Shuang Ren^{1

2

3}, Fengyuan Zhao^{1

2

3}, Hongde Wang^{1

2

3}, Ping Liu^{1

2

3}, Jianquan Wang^{1

2

3}, Xiaoqing Hu^{1

2

3}, Yingfang Ao^{1

2

3}

Affiliations

¹ Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing, China.
² Beijing Key Laboratory of Sports Injuries, Beijing, China.
³ Engineering Research Center of Sports Trauma Treatment Technology and Devices, Ministry of Education, Beijing, China.

Abstract

The effective and translational strategy to regenerate knee meniscal fibrocartilage remained challenging. Herein, we first identified vascular smooth muscle cells (VSMCs) transdifferentiated into fibrochondrocytes and participated in spontaneous meniscal regeneration using smooth muscle cell lineage tracing transgenic mice meniscal defect model. Then, we identified low-intensity pulsed ultrasound (LIPUS) acoustic stimulus enhanced fibrochondrogenic transdifferentiation of VSMCs in vitro and in vivo. Mechanistically, LIPUS stimulus could up-regulate mechanosensitive ion channel Piezo1 expression and then activate the transforming growth factor β1 (TGFβ1) signal, following repression of the Notch signal, consequently enhancing fibrochondrogenic transdifferentiation of VSMCs. Finally, we demonstrated that the regular LIPUS stimulus enhanced anisotropic native-like meniscal fibrocartilage tissue regeneration in a beagle canine subtotal meniscectomy model at 6 months postoperatively. The single-cell RNA sequencing analysis confirmed the role of VSMC fibrochondrogenic transdifferentiation in meniscal regeneration.