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Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression

by Li, Fangfei , Lu, Aiping , Huang, Guangxin , Zhang, Huarui , Zhang, Zongkang , Zhang, Ge , Yu, Yuanyuan , Chen, Lin , Liu, Jin , Liang, Chao , Wu, Xiaohao , Dang, Lei , Zhong, Chuanxin , Zhang, Bao-Ting , Li, Dijie , Lu, Jun

in Angiogenesis / Animals / Arthritis / Cartilage / Chondrocytes / Mice / MicroRNAs / MicroRNAs - genetics / Osteoarthritis / Osteoarthritis - genetics / Osteoclasts / Surgery / Tissue Inhibitor of Metalloproteinase-2

2021

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Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression

2021

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Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression

2021

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Journal Article

Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression

Li, Fangfei,

Lu, Aiping,

Huang, Guangxin,

Zhang, Huarui,

Zhang, Zongkang,

Zhang, Ge,

Yu, Yuanyuan,

Chen, Lin,

Liu, Jin,

Liang, Chao,

Wu, Xiaohao,

Dang, Lei,

Zhong, Chuanxin,

Zhang, Bao-Ting,

Li, Dijie,

Lu, Jun

2021

Overview

Osteoarthritis (OA) is a prevalent aging-related joint disease lacking disease-modifying therapies. Here, we identified an upregulation of circulating exosomal osteoclast (OC)-derived microRNAs (OC-miRNAs) during the progression of surgery-induced OA in mice. We found that reducing OC-miRNAs by Cre-mediated excision of the key miRNA-processing enzyme Dicer or blocking the secretion of OC-originated exosomes by short interfering RNA-mediated silencing of Rab27a substantially delayed the progression of surgery-induced OA in mice. Mechanistically, the exosomal transfer of OC-miRNAs to chondrocytes reduced the resistance of cartilage to matrix degeneration, osteochondral angiogenesis and sensory innervation during OA progression by suppressing tissue inhibitor of metalloproteinase-2 (TIMP-2) and TIMP-3. Furthermore, systemic administration of a new OC-targeted exosome inhibitor (OCExoInhib) blunted the progression of surgery-induced OA in mice. We suggest that targeting the exosomal transfer of OC-miRNAs to chondrocytes represents a potential therapeutic avenue to tackle OA progression.

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Publisher

Nature Publishing Group

Subject

/ Animals

/ Mice