CircStrn3 targeting microRNA-9-5p is involved in the regulation of cartilage degeneration and subchondral bone remodelling in osteoarthritis

Bin Li; Tao Ding; Haoyi Chen; Changwei Li; Bo Chen; Xing Xu; Ping Huang; Fangqiong Hu; Lei Guo

doi:10.1302/2046-3758.121.BJR-2022-0231.R1

CircStrn3 targeting microRNA-9-5p is involved in the regulation of cartilage degeneration and subchondral bone remodelling in osteoarthritis

Bone Joint Res. 2023 Jan;12(1):33-45. doi: 10.1302/2046-3758.121.BJR-2022-0231.R1.

Authors

Bin Li¹, Tao Ding¹, Haoyi Chen¹, Changwei Li¹, Bo Chen¹, Xing Xu¹, Ping Huang¹, Fangqiong Hu¹, Lei Guo¹

Affiliation

¹ Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

PMID: 36642417
PMCID: PMC9872037
DOI: 10.1302/2046-3758.121.BJR-2022-0231.R1

Abstract

Aims: Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods: Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.

Results: Tensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively 'sponging' miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice.

Conclusion: Taken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA.Cite this article: Bone Joint Res 2023;12(1):33-45.

Keywords: CircStrn3; Exosome; Kruppel-like factor 5; Osteoarthritis; Osteoarthritis (OA); Quantitative real-time polymerase chain reaction; RNAs; cartilage degeneration; cartilage tissues; chondrocytes; microRNA-9-5p; microRNAs (miRNAs); osteoblasts; strain; subchondral bone.