miR-204 ameliorates osteoarthritis pain by inhibiting SP1-LRP1 signaling and blocking neuro-cartilage interaction

Ke Lu; Qingyun Wang; Liuzhi Hao; Guizheng Wei; Tingyu Wang; William W Lu; Guozhi Xiao; Liping Tong; Xiaoli Zhao; Di Chen

doi:10.1016/j.bioactmat.2023.03.010

miR-204 ameliorates osteoarthritis pain by inhibiting SP1-LRP1 signaling and blocking neuro-cartilage interaction

Bioact Mater. 2023 Mar 20:26:425-436. doi: 10.1016/j.bioactmat.2023.03.010. eCollection 2023 Aug.

Authors

Ke Lu^{1

2}, Qingyun Wang^{1

2}, Liuzhi Hao³, Guizheng Wei^{1

2}, Tingyu Wang⁴, William W Lu^{2

5}, Guozhi Xiao⁶, Liping Tong¹, Xiaoli Zhao³, Di Chen^{1

2}

Affiliations

¹ Research Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
² Faculty of Pharmaceutical Sciences, Shenzhen Institute of Advanced Technology, Shenzhen, 518055, China.
³ Research Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
⁴ Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200011, China.
⁵ Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong 999077, China.
⁶ School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.

Abstract

Osteoarthritis (OA) is a painful degenerative joint disease and is the leading cause of chronic disability among elderly individuals. To improve the quality of life for patients with OA, the primary goal for OA treatment is to relieve the pain. During OA progression, nerve ingrowth was observed in synovial tissue and articular cartilage. These abnormal neonatal nerves act as nociceptors to detect OA pain signals. The molecular mechanisms for transmitting OA pain in the joint tissues to the central nerve system (CNS) is currently unknown. MicroRNA miR-204 has been demonstrated to maintain the homeostasis of joint tissues and have chondro-protective effect on OA pathogenesis. However, the role of miR-204 in OA pain has not been determined. In this study, we investigated interactions between chondrocytes and neural cells and evaluated the effect and mechanism of miR-204 delivered by exosome in the treatment of OA pain in an experimental OA mouse model. Our findings demonstrated that miR-204 could protect OA pain by inhibition of SP1- LDL Receptor Related Protein 1 (LRP1) signaling and blocking neuro-cartilage interaction in the joint. Our studies defined novel molecular targets for the treatment of OA pain.

Keywords: LRP1; Neuro-cartilage interaction; Osteoarthritis; Pain; miR-204.