miR‐181c‐5p mediates simulated microgravity‐induced impaired osteoblast proliferation by promoting cell cycle arrested in the G₂ phase

Abstract

Impaired osteoblast proliferation plays fundamental roles in microgravity‐induced bone loss, and cell cycle imbalance may result in abnormal osteoblast proliferation. However, whether microgravity exerts an influence on the cell cycle in osteoblasts or what mechanisms may underlie such an effect remains to be fully elucidated. Herein, we confirmed that simulated microgravity inhibits osteoblast proliferation. Then, we investigated the effect of mechanical unloading on the osteoblast cell cycle and found that simulated microgravity arrested the osteoblast cell cycle in the G 2 phase. In addition, our data showed that cell cycle arrest in osteoblasts from simulated microgravity was mainly because of decreased cyclin B1 expression. Furthermore, miR‐181c‐5p directly inhibited cyclin B1 protein translation by binding to a target site in the 3′UTR. Lastly, we demonstrated that inhibition of miR‐181c‐5p partially counteracted cell cycle arrest and decreased the osteoblast proliferation induced by simulated microgravity. In conclusion, our study demonstrates that simulated microgravity inhibits cell proliferation and induces cell cycle arrest in the G 2 phase in primary mouse osteoblasts partially through the miR‐181c‐5p/cyclin B1 pathway. This work may provide a novel mechanism of microgravity‐induced detrimental effects on osteoblasts and offer a new avenue to further investigate bone loss induced by mechanical unloading.

Effect of Unloading Condition on the Healing Process and Effectiveness of Platelet Rich Plasma as a Countermeasure: Study on In Vivo and In Vitro Wound Healing Models

“…To our knowledge, an increase in apoptosis has never been described in fibroblasts cultured in real or modeled µg, and we did not observe necrosis and/or apoptotic bodies in fibroblast cultures (see Figure 7). Sun et al [51] reported that µg-induced reduction in osteoblast proliferation is because of an arrest in cell cycle progression. In agreement with Sun, in experiments on fibroblasts cultured in µg, modeled by a rotating cell culture system (RCCS), we found a temporary arrest of the cell cycle, with repercussion on proliferation (data not yet published).…”

Unique, Gender-Dependent Serum microRNA Profile in PLS3 Gene-Related Osteoporosis

“…First, miR-181c-5p, which relates to postmenopausal osteoporosis and fracture risk in diabetic patients, (13,15,35) inhibits osteoblast proliferation in simulated microgravity-settings through interactions with cyclin B1. (36) Here, we could experimentally validate the interaction between miR-181c-5p and PLS3. Second, miR-203a-3p is reported to regulate osteoblast differentiation through repressing DLX5 and RUNX2 in traumatic heterotopic ossification and in bone lesions of metastatic breast cancer, (37)(38)(39) and to inhibit osteogenesis in diabetic rats' jaw bones.…”

A Protective Strategy to Counteract the Oxidative Stress Induced by Simulated Microgravity on H9C2 Cardiomyocytes

“…The microgravity-induced decrease in cell proliferation was also seen in other cell phenotypes [22,32,48,49]. However, there are controversial evidences about the effects of microgravity on cell growth in stem cells and cardiomyocytes differentiating from pluripotent stem cells [50][51][52][53][54]. These introduce the hypothesis that the effects induced by microgravity are not only phenotype-dependent but also dependent on the functional and metabolic status of the cells tested.…”