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A novel long noncoding RNA AK016739 inhibits osteoblast differentiation and bone formation

Chong Yin  ^{1   2   3} , Ye Tian  ^{1   2   3} , Yang Yu  ⁴ , Haoyu Wang  ⁵ , Zhixiang Wu  ^{1   2   3} , Zizhan Huang  ^{1   2   3} , Yan Zhang  ^{1   2   3} , Dijie Li  ^{1   2   3} , Chaofei Yang  ^{1   2   3} , Xue Wang  ^{1   2   3} , Yu Li  ^{1   2   3} , Airong Qian  ^{1   2   3}

• ¹ Laboratory for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China.
• ² Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China.
• ³ NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi’an, China.
• ⁴ Tianjin Key Laboratory on Technologies Enabling Development Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
• ⁵ Department of Software Technology and Service Engineering, School of Software and Microelectronics, Peking University, Beijing, China.

Abstract

The incidence of postmenopausal osteoporosis research 50% in middle-aged and older women, however, effects of existing therapy are not ideal. Emerging evidence have proved that long noncoding RNAs (lncRNAs) was correlated with multiple physiological and pathology processes including development, carcinogenesis, and osteogenesis. However, reports on lncRNAs regulating bone formation were relatively limited. In this study, we screened osteogenic lncRNAs through mRNA/lncRNA microarray combined with gene coexpression analysis. The biological function of the screened lncRNA was assessed both in vitro and in vivo. The effects of the lncRNA on osteogenic transcription factors were also evaluated. We identified AK016739, which was correlated with osteogenic differentiation and enriched in skeletal tissues of mice. The expression levels of AK016739 in bone-derived mesenchymal stem cells were increased with age and negatively correlated with osteogenic differentiation marker genes. Experiments showed that AK016739 inhibited osteoblast differentiation, and in vivo inhibition of AK016739 by its small interfering RNA would rescue bone formation in ovariectomized osteoporosis mice model. In addition, AK016739 suppressed both expression levels and activities of osteogenic transcription factors. This newly identified lncRNA AK016739 has revealed a new mechanism of osteogenic differentiation and provided new targets for treatment of skeletal disorders.

Keywords: AK016739; bone formation; lncRNA; osteoblast differentiation; postmenopausal osteoporosis; transcript factor.