HOTAIRM1 promotes osteogenic differentiation and alleviates osteoclast differentiation by inactivating the NF-κB pathway.


Ren Y(1), Zhang K(1), Wang J(1), Meng X(1), Du X(1), Shi Z(1), Xue Y(2), Hong W(1)(3).
Author information:
(1)Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
(2)Department of Orthopedic Surgery, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300070, China.
(3)Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease of Ministry of Education, Tianjin Medical University, Tianjin 300070, China.


Osteoporosis (OP), one of the most prevalent chronic progressive bone diseases, is caused by deficiency in bone formation by osteoblasts or excessive bone resorption by osteoclasts and subsequently increases the risk of bone fractures. Emerging evidence has indicated that long noncoding RNAs (lncRNAs) play key roles in many biological processes and various disorders. However, the role and mechanism of HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), a myeloid-specific lncRNA, in osteoclast differentiation, osteogenic differentiation, and OP remain unclear. In this study, we found that HOTAIRM1 was upregulated during ossification of ligamentum flavum and osteogenic differentiation, while it was downregulated in osteoclast differentiation and in the bone and serum of human and mouse with OP. Further investigation revealed that silencing Hotairm1 decreased the expression of the osteogenic markers and attenuated osteogenesis. Moreover, forced Hotairm1 expression inhibited the expressions of the osteoclastogenesis markers and alleviated receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation. Mechanically, Hotairm1 repressed the phosphorylation of p65 and inhibitor of κBα (IκBα) and attenuated RANKL-mediated enhancement of phos-p65 and IκBα, suggesting that Hotairm1 inhibits RANKL-induced osteoclastogenesis through the NF-κB pathway. In conclusion, our data identified a crucial role of HOTAIRM1 in OP, providing a proof of this molecule as a potential diagnostic marker and a possible therapeutic target against OP.