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LncRNA AK077216 promotes RANKL‐induced osteoclastogenesis and bone resorption via NFATc1 by inhibition of NIP45
Author(s) -
Liu Chuan,
Cao Zhen,
Bai Yun,
Dou Ce,
Gong Xiaoshan,
Liang Mengmeng,
Dong Rui,
Quan Hongyu,
Li Jianmei,
Dai Jingjin,
Kang Fei,
Zhao Chunrong,
Dong Shiwu
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27031
Subject(s) - osteoclast , bone resorption , rankl , downregulation and upregulation , microbiology and biotechnology , osteopetrosis , cathepsin k , biology , transcription factor , osteoimmunology , cancer research , chemistry , immunology , endocrinology , biochemistry , gene , activator (genetics) , in vitro
Osteoclasts derived from the monocyte/macrophage hematopoietic lineage regulate bone resorption, a process balanced by bone formation in the continual renewal of the skeletal system. As dysfunctions of these cells result in bone metabolic diseases such as osteoporosis and osteopetrosis, the exploration of the mechanisms regulating their differentiation is a priority. A potential mechanism may involve long noncoding RNAs (lncRNAs), which are known to regulate various cell biology activities, including proliferation, differentiation, and apoptosis. The expression of the lncRNA AK077216 (Lnc‐AK077216) is significantly upregulated during osteoclastogenesis identified by microarray and verified by qPCR. Up‐ and downregulation of Lnc‐AK077216, respectively promotes and inhibits osteoclast differentiation, bone resorption, and the expression of related genes on the basis of tartrate‐resistant acid phosphatase staining, qPCR, and western blot results. In addition, Lnc‐AK077216 suppresses NIP45 expression and promotes the expression of NFATc1, an essential transcription factor during osteoclastogenesis. Besides, it was found that the expression of Lnc‐AK077216 and Nfatc1 is upregulated, whereas Nip45 expression is downregulated in bone marrow and spleen tissues of ovariectomized mice. The results suggest that Lnc‐AK077216 regulates NFATc1 expression and promotes osteoclast formation and function, providing a novel mechanism of osteoclastogenesis and a potential biomarker or a new drug target for osteoporosis.