Abstract
Ameliorating bone loss caused by mechanical unloading is a substantial clinical challenge, and the role of noncoding RNAs in this process has attracted increasing attention. In this study, we found that the long noncoding RNA osteoblast differentiation-related lncRNA under simulated microgravity (lncRNA ODSM) could inhibit osteoblast apoptosis and promote osteoblast mineralization in vitro. The increased expression level of the lncRNA ODSM partially reduced apoptosis and promoted differentiation in MC3T3-E1 cells under microgravity unloading conditions, and the effect was partially dependent on miR-139-3p. LncRNA ODSM supplementation in hindlimb-unloaded mice caused a decrease in the number of apoptotic cells in bone tissue and an increase in osteoblast activity. Furthermore, targeted overexpression of the lncRNA ODSM in osteoblasts partially reversed bone loss induced by mechanical unloading at the microstructural and biomechanical levels. These findings are the first to suggest the potential value of the lncRNA ODSM in osteoporosis therapy and the treatment of pathological osteopenia.
Highlights
Bone is a dynamic tissue that is constantly resorbed by osteoclasts and reconstructed by osteoblasts[1,2]
LncRNA ODSM inhibits osteoblast apoptosis and promotes osteoblast mineralization The Long noncoding RNAs (lncRNAs) ODSM expression level was much higher in the femurs than in other tissues and organs in mice, and the level of the lncRNA ODSM was significantly decreased in the femurs of HU mice (Supplementary Fig. 1)
Silencing the lncRNA ODSM markedly increased the ratio of apoptotic osteoblasts in the small interfering RNA-ODSM group (Fig. 1a)
Summary
Bone is a dynamic tissue that is constantly resorbed by osteoclasts and reconstructed by osteoblasts[1,2]. Osteoporosis is associated with a number of stimuli, including hormone fluctuations, nutrition, and inflammatory and mechanical loading[3,4,5]. Mechanical loads have been considered the basis for the normal development and maintenance of the musculoskeletal system. Long-term bed rest due to spinal injury or other injuries, as well as the reduction in bone loading caused by the microgravity (MG) environment during space flight, results in bone loss[5,6,7]. Hindlimb-unloaded (HU) animal models are the Clinostats, random positioning machines, or rotary wall vessels are usually used to study cell responses to conditions lacking mechanical loading[12,13,14]. It is necessary and feasible to further study the molecular mechanisms regulating osteoblast function in the unloading environment and to subsequently develop a promising strategy for bone formation
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