The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression

Jian Huang, Lan Zhao, Yunshan Fan, Lifan Liao, Peter X. Ma, Guozhi Xiao and Di Chen ()
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Jian Huang: Rush University Medical Center
Lan Zhao: Rush University Medical Center
Yunshan Fan: Rush University Medical Center
Lifan Liao: Rush University Medical Center
Peter X. Ma: University of Michigan
Guozhi Xiao: Rush University Medical Center
Di Chen: Rush University Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Osteoarthritis (OA) is a common, painful disease. Currently OA is incurable, and its etiology largely unknown, partly due to limited understanding of OA as a whole-joint disease. Here we report that two homologous microRNAs, miR-204 and miR-211, maintain joint homeostasis to suppress OA pathogenesis. Specific knockout of miR-204/-211 in mesenchymal progenitor cells (MPCs) results in Runx2 accumulation in multi-type joint cells, causing whole-joint degeneration. Specifically, miR-204/-211 loss-of-function induces matrix-degrading proteases in articular chondrocytes and synoviocytes, stimulating articular cartilage destruction. Moreover, miR-204/-211 ablation enhances NGF expression in a Runx2-dependent manner, and thus hyper-activates Akt signaling and MPC proliferation, underlying multiplex non-cartilaginous OA conditions including synovial hyperplasia, osteophyte outgrowth and subchondral sclerosis. Importantly, miR-204/-211-deficiency-induced OA is largely rescued by Runx2 insufficiency, confirming the miR-204/-211-Runx2 axis. Further, intraarticular administration of miR-204-expressing adeno-associated virus significantly decelerates OA progression. Collectively, miR-204/-211 are essential in maintaining healthy homeostasis of mesenchymal joint cells to counteract OA pathogenesis.

Date: 2019
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DOI: 10.1038/s41467-019-10753-5

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