Silencing of lncRNA AK045490 Promotes Osteoblast Differentiation and Bone Formation via β-Catenin/TCF1/Runx2 Signaling Axis

Dijie Li  ^{1   2   3   4} , Ye Tian  ^{1   2   3} , Chong Yin  ^{1   2   3} , Ying Huai  ^{1   2   3} , Yipu Zhao  ^{1   2   3} , Peihong Su  ^{1   2   3} , Xue Wang  ^{1   2   3} , Jiawei Pei  ^{1   2   3} , Kewen Zhang  ^{1   2   3} , Chaofei Yang  ^{1   2   3} , Kai Dang  ^{1   2   3} , Shanfeng Jiang  ^{1   2   3} , Zhiping Miao  ^{1   2   3} , Meng Li  ⁵ , Qiang Hao  ⁵ , Ge Zhang  ^{4   6} , Airong Qian  ^{1   2   3} Affiliations

• PMID: 31835596
• PMCID: PMC6941011
• DOI: 10.3390/ijms20246229

Free PMC article

Abstract

Osteoporosis, a disease characterized by both loss of bone mass and structural deterioration of bone, is the most common reason for a broken bone among the elderly. It is known that the attenuated differentiation ability of osteogenic cells has been regarded as one of the greatest contributors to age-related bone formation reduction. However, the effects of current therapies are still unsatisfactory. In this study we identify a novel long noncoding RNA AK045490 which is correlated with osteogenic differentiation and enriched in skeletal tissues of mice. In vitro analysis of bone-derived mesenchymal stem cells (BMSCs) showed that AK045490 inhibited osteoblast differentiation. In vivo inhibition of AK045490 by its small interfering RNA rescued bone formation in ovariectomized osteoporosis mice model. Mechanistically, AK045490 inhibited the nuclear translocation of β-catenin and downregulated the expression of TCF1, LEF1, and Runx2. The results suggest that Lnc-AK045490 suppresses β-catenin/TCF1/Runx2 signaling and inhibits osteoblast differentiation and bone formation, providing a novel mechanism of osteogenic differentiation and a potential drug target for osteoporosis.

Keywords: AK045490; bone formation; lncRNA; osteoblast differentiation; osteoporosis; transcript factor.