Long noncoding RNA Gm31629 promotes bone regeneration by maintaining bone marrow mesenchymal stem cells activity

Long noncoding RNA Gm31629 can regulate hypothalamic neural stem cells (htNSCs) senescence and the aging process. However, the effect of Gm31629 on the senescence of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration is unclear. In the present study, we investigated the effects of Gm31629 on the senescence of BMSCs and bone regeneration.

Gm31629 knockout (Gm31629-KO) and wild-type (WT) mice were used to establish a bone regeneration model. The Brdu labelling, CCK8 assay, wound healing assay, β-gal staining and osteogenic differentiation assay were used to assess the effects of Gm31629 on the functions of BMSCs. Micro-computed tomography (CT), histochemical and immunohistochemical staining were used to evaluate the ability of bone regeneration. The mimic of Gm31629, theaflavin 3-gallate, was used to investigate its role on the senescence of BMSCs and bone regeneration.

The expression of Gm31629 reduced in BMSCs of middle-aged mice was compared with that of young mice. The deletion of Gm31629 was sufficient to drive the senescence of BMSCs, resulting in impaired bone regeneration in mice. Mechanistically, Gm31629 could interact with Y-box protein 1(YB-1) and delay its degradation, decreasing the transcription of p16 of BMSCs. We also found that theaflavin 3-gallate could alleviate the senescence of BMSCs and promote bone regeneration in middle-aged mice.

These results indicated that Gm31629 played an important role on BMSCs senescence and bone regeneration and provided a therapeutic target to promote bone regeneration.