J Bone Miner Res. 2020 Apr 30. doi: 10.1002/jbmr.4039. [Epub ahead of print]
Increasing evidence uncover the essential role of lncRNAs in bone metabolism and the association of lncRNA with genetic risk of osteoporosis. However, whether lncRNA Neat1 is involved remains largely unknown. In the present study, we found that Neat1 is induced by osteoclastic differentiation stimuli. Knockdown of Neat1 attenuates osteoclast formation whereas overexpression of Neat1 accelerates osteoclast formation. In vivo evidence demonstrated that enhanced Neat1 expression stimulates osteoclastogenesis and reduces bone mass in mice. Mechanically, Neat1 competitively binds with miR-7 and blocks its function for regulating PTK2. Intergenic SNP rs12789028 acts as allele-specific long-range enhancer for NEAT1 via chromatin interactions. We establish for the first time that Neat1 plays an essential role in osteoclast differentiation, and provide genetic mechanism underlying the association of NEAT1 locus with osteoporosis risk. These results enrich the current knowledge of NEAT1 function, and uncover the potential of NEAT1 as a therapeutic target for osteoporosis.