LncRNA‐Jak3:Jak3 coexpressed pattern regulates monosodium urate crystal‐induced osteoclast differentiation through Nfatc1/Ctsk expression

• Published in: Environmental toxicology Vol. 34; no. 2; pp. 179 - 187
• Main Authors: Lee, Chi‐Pin, Huang, Yu‐Nan, Nithiyanantham, Srinivasan, Huang, Chung‐Ming, Ko, Ying‐Chin
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2019; Wiley Subscription Services, Inc
• Subjects: Animals; Biocompatibility; bone erosion; Cathepsin K; Cathepsin K - genetics; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cells; Differentiation; DNA microarrays; drugs; Gene expression; Gene Expression Regulation - drug effects; Gene regulation; Gout; Gout - metabolism; gouty arthritis; HEK293 Cells; Humans; Inflammation; Inflammatory response; Janus Kinase 3 - genetics; Leukocytes (mononuclear); LncRNA‐Jak3; messenger RNA; Mice; microarray technology; MSU; NFATC Transcription Factors - genetics; osteoclast differentiation; Osteoclastogenesis; Osteoclasts; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteogenesis - drug effects; Osteogenesis - genetics; patients; Post-transcription; RAW 264.7 Cells; regulator genes; RNA, Long Noncoding - genetics; T-lymphocytes; therapeutics; transcription (genetics); Uric acid; Uric Acid - metabolism; Uric Acid - toxicity; LncRNA-Jak3; osteoclast differentiation; gouty arthritis; bone erosion; MSU
• ISSN: 1520-4081; 1522-7278; 1522-7278
• DOI: 10.1002/tox.22672

LncRNA transcripts have been emerged as gene regulators through transcriptional and posttranscriptional regulation. Monosodium urate monohydrate (MSU) elicits inflammatory response and a critical regulator of bone erosion in gout. The aim of this study is to clarify the pro‐osteogenic role of LncRNA in MSU‐induced osteoclast differentiation. We performed microarray analysis to identify stage specific expressions of LncRNA and mRNA during osteoclast differentiation in RAW264.7 cells. Among the 314 pairs of LncRNA‐mRNA coexpressed patterns in the osteoclast lineage, 22 pairs revealed to have inflammatory function. Importantly, LncRNA‐Jak3 and Jak3 co‐expression patterns were significantly upregulated in the osteoclasts. In specific, Jak3 contributes to MSU‐induced osteoclasts differentiation by positively regulating expression of the osteoclast factor, nuclear factor of activated T‐cells 1 (Nfatc1). Mechanistically, LncRNA‐Jak3‐mediated Nfatc1 activation upregulated cathepsin K (Ctsk) expressions. LncRNA‐Jak3 knockdown abolished formation of MSU‐induced mature osteoclasts. In addition, we found that gout patients showed increased levels of LncRNA‐Jak3 in the mononuclear cells. Our data demonstrate that the critical functional role of LncRNA‐Jak3 in osteoclast differentiation via Jak3/Nfatc1/Ctsk axis. Finally, characterization of these regulatory networks is likely to reveal novel drug targets and opportunities for therapeutic intervention in bone erosion.