Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

Abstract

Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identified a novel lncRNA, OGRU, a 1816-nucleotide transcript with significantly decreased levels in bone specimens from hindlimb-unloaded mice and in MC3T3-E1 cells under clinorotation unloading conditions. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading conditions and attenuated the suppression of MC3T3-E1 cell differentiation induced by clinorotation unloading. Furthermore, this study found that supplementation of pcDNA3.1(+)-OGRU via (DSS) 6 -liposome delivery to the bone formation surfaces of hindlimb-unloaded (HLU) mice partially alleviated unloading-induced bone loss. Mechanistic investigations demonstrated that OGRU can function as a competing endogenous RNA (ceRNA) to facilitate the protein expression of Hoxa10 by competitively binding miR-320-3p and subsequently promote osteoblast differentiation and bone formation. Taken together, the results of our study provide the first clarification of the role of the OGRU in unloading-induced bone loss through the miR-320-3p/Hoxa10 axis, suggesting an efficient anabolic strategy for osteoporosis treatment.

Obesity regulates miR‐467/HoxA10 axis on osteogenic differentiation and fracture healing by BMSC‐derived exosome LncRNA H19

“…Studies have shown that Hoxa10 can participate in the research of regulating osteogenic differentiation. Increased expression can promote bone repair and osteogenic differentiation 25‐27 . Similarly, previous studies have confirmed that high‐fat diet can reduce the expression of Hoxa10 in mice and inhibit bone development 28 .…”