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

Lu，Ke1,2; Wang，Qingyun1,2; Hao，Liuzhi3; Wei，Guizheng1,2; Wang，Tingyu4; Lu，William W.2,5; Xiao，Guozhi6; Tong，Liping1; Zhao，Xiaoli3; Chen，Di1,2

2023-08-01

10.1016/j.bioactmat.2023.03.010

Bioactive Materials   影响因子和分区

2452-199X

2452-199X

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.

LRP1 miR-204 Neuro-cartilage interaction Osteoarthritis Pain

SCI

英语

其他

National Key Research and Development Program of China[2021YFB3800800] ; National Natural Science Foundation of China (NSFC)["82030067","82161160342","82250710174","82172397","81874011"] ; Hong Kong RGC[HKU-17101821]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000973264900001

KEAI PUBLISHING LTD

2-s2.0-85150185927

Scopus

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,Hong Kong
6.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Lu，Ke,Wang，Qingyun,Hao，Liuzhi,et al. miR-204 ameliorates osteoarthritis pain by inhibiting SP1-LRP1 signaling and blocking neuro-cartilage interaction[J]. Bioactive Materials,2023,26:425-436.

Lu，Ke.,Wang，Qingyun.,Hao，Liuzhi.,Wei，Guizheng.,Wang，Tingyu.,...&Chen，Di.(2023).miR-204 ameliorates osteoarthritis pain by inhibiting SP1-LRP1 signaling and blocking neuro-cartilage interaction.Bioactive Materials,26,425-436.

Lu，Ke,et al."miR-204 ameliorates osteoarthritis pain by inhibiting SP1-LRP1 signaling and blocking neuro-cartilage interaction".Bioactive Materials 26(2023):425-436.