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- Title
Involvement of microRNA-23b in TNF-α-reduced BMSC osteogenic differentiation via targeting runx2.
- Authors
Deng, Lin; Hu, Guoli; Jin, Lei; Wang, Chenglong; Niu, Hongwen
- Abstract
Elucidation of the molecular mechanism governing bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation is of great importance for improving the treatment of osteoporosis. TNF-α is a well-known inhibitory factor during osteogenic differentiation of BMSCs. In our experiment, we consistently observed that TNF-α significantly inhibited BMSC osteogenic differentiation, which was partially rescued by BAY 11-7082 (NF-κB inhibitor). In this study, we examined the potential roles of microRNAs (miRNAs) involved in TNF-α-mediated reduction of BMSC osteogenesis. We found that microRNA-23b (miR-23b) was dramatically induced under the stimulation of TNF-α, which was abolished by BAY 11-7082. Similar to the effect of TNF-α, miR-23b agonist (agomir-23b) obviously impaired BMSC osteogenic differentiation in vitro and in vivo. However, agomir-23b had no effect on osteoclast activity. Overexpression of miR-23b significantly reduced runx2, the master transcription factor during osteogenesis, suggesting that miR-23b acts as an endogenous attenuator of runx2 in BMSCs. Mutation of the putative miR-23b binding site in runx2 mRNA blocked miR-23b-mediated repression of the runx2 3' untranslated region (3'UTR) luciferase reporter activity, suggesting that miR-23b directly binds to runx2 3'UTR. Furthermore, infection with Ad-runx2 (adenovirus carrying the entire CDS sequence of runx2) effectively rescued the inhibition of BMSC osteogenic differentiation in miR-23b-overexpressing cells, indicating that the inhibiting effect of miR-23b on osteogenesis is mediated by suppression of runx2. Moreover, caudal vein injection of agomir-23b notably caused severe osteoporosis in mice, and forced expression of runx2 by combined injecting Ad-runx2 attenuated the bone loss induced by miR-23b. Collectively, these data indicated that miR-23b was involved in TNF-α-mediated reduction of BMSC osteogenesis by targeting runx2. These findings may provide new insights into understanding the regulatory role of miR-23b in the process of BMSC osteogenic differentiation in inflammatory conditions and a novel therapeutic target for osteoporosis.
- Subjects
BONE marrow; MESENCHYMAL stem cells; BONE growth; OSTEOINDUCTION; OSTEOPOROSIS; PROTEIN metabolism; RNA metabolism; ANIMAL experimentation; BIOCHEMISTRY; BONE resorption; CELL differentiation; PHENOMENOLOGY; MICE; NUCLEOTIDES; PROTEINS; RNA; TUMOR necrosis factors
- Publication
Journal of Bone & Mineral Metabolism, 2018, Vol 36, Issue 6, p648
- ISSN
0914-8779
- Publication type
journal article
- DOI
10.1007/s00774-017-0886-8