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

Liu，Jin1,2,3,4,5; Wu，Xiaohao1; Lu，Jun1,5,6; Huang，Guangxin7; Dang，Lei1,4,5; Zhang，Huarui1,4; Zhong，Chuanxin1,4,8; Zhang，Zongkang9; Li，Dijie1,10; Li，Fangfei1,2,3,4,5; Liang，Chao1,2,3,4,5; Yu，Yuanyuan1,2,3,4,5; Zhang，Bao Ting9; Chen，Lin11; Lu，Aiping1,2,3,4,5; Zhang，Ge1,2,3,4,5

2021-04-01

10.1038/s43587-021-00050-6

Nature Aging   Impact Factor & Quartile

2662-8465

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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2-s2.0-85118931914

Scopus

1.Law Sau Fai Institute for Advancing Translational Medicine in Bone & Joint Diseases,Hong Kong Baptist University,Hong Kong
2.Institute of Integrated Bioinfomedicine and Translational Science,Hong Kong Baptist University,Hong Kong
3.Institute of Precision Medicine and Innovative Drug Discovery,Hong Kong Baptist University,Hong Kong
4.School of Chinese Medicine,Hong Kong Baptist University,Hong Kong
5.Shenzhen Institute for Research and Continuing Education (IRACE),Hong Kong Baptist University,Shenzhen,China
6.School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu,China
7.Department of Joint Surgery,The Third Affiliated Hospital of Southern Medical University,The Third School of Clinical Medicine,Southern Medical University,Guangzhou,China
8.Department of Materials Science and Engineering,Southern University of Science and Technology,Shenzhen,China
9.School of Chinese Medicine,Faculty of Medicine,Chinese University of Hong Kong,Hong Kong
10.School of Life Sciences,Northwestern Polytechnical University,Xi’an,China
11.Laboratory of Wound Repair and Rehabilitation,State Key Laboratory of Trauma,Burns and Combined Injury,Trauma Center,Research Institute of Surgery,Daping Hospital,Army Medical University,Chongqing,China

Liu，Jin,Wu，Xiaohao,Lu，Jun,et al. Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression[J]. Nature Aging,2021,1(4):368-384.

Liu，Jin.,Wu，Xiaohao.,Lu，Jun.,Huang，Guangxin.,Dang，Lei.,...&Zhang，Ge.(2021).Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression.Nature Aging,1(4),368-384.

Liu，Jin,et al."Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression".Nature Aging 1.4(2021):368-384.