Drs. Wang and Chung contributed equally to this work.
MicroRNA-29a Protects Against Glucocorticoid-Induced Bone Loss and Fragility in Rats by Orchestrating Bone Acquisition and Resorption
Article first published online: 30 MAY 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 6, pages 1530–1540, June 2013
How to Cite
Wang, F.-S., Chung, P.-C., Lin, C.-L., Chen, M.-W., Ke, H.-J., Chang, Y.-H., Chen, Y.-S., Wu, S.-L. and Ko, J.-Y. (2013), MicroRNA-29a Protects Against Glucocorticoid-Induced Bone Loss and Fragility in Rats by Orchestrating Bone Acquisition and Resorption. Arthritis & Rheumatism, 65: 1530–1540. doi: 10.1002/art.37948
- Issue published online: 30 MAY 2013
- Article first published online: 30 MAY 2013
- Accepted manuscript online: 25 MAR 2013 12:00AM EST
- Manuscript Accepted: 14 MAR 2013
- Manuscript Received: 5 APR 2012
- National Health Research Institute, Taiwan. Grant Number: NHRI-EX101-10140EI
- Chang Gung Memorial Hospital, Taiwan. Grant Numbers: CMRPG8A0911, CMRPG8B0871
Vol. 66, Issue 4, 989, Article first published online: 28 MAR 2014
Excessive glucocorticoid treatment increases the incidence of osteopenia and osteonecrosis. MicroRNAs (miRNAs) reportedly target messenger RNA expression and regulate osteoblastogenesis and skeletal development. We undertook this study to investigate whether miR-29a regulates glucocorticoid-mediated bone loss.
Rats were given methylprednisolone, lentivirus-mediated miR-29a precursor, or lentivirus-mediated miR-29a inhibitor. Dual x-ray absorptiometry, micro–computed tomography, material testing, and enzyme-linked immunosorbent assay were performed to quantify bone mass, microarchitecture, peak load, and serum Dkk-1 levels. Differential miRNA expression profiles were detected using polymerase chain reaction arrays. The abundance of signaling molecules was assessed using immunoblotting.
Glucocorticoid treatment induced loss of bone mineral density and trabecular microstructure in association with reduced miR-29a expression. Treatment with miR-29a precursor attenuated the adverse effects of glucocorticoid on bone mass, trabecular bone volume fraction, and biomechanical load-bearing capacity of bone tissue. Gain of miR-29a function alleviated the detrimental effects of glucocorticoid treatment on mineral acquisition and ex vivo osteoblast differentiation, and also reduced osteoclast surface, ex vivo osteoclast differentiation, and RANKL expression in bone microenvironments. Knockdown of miR-29a accelerated osteoclast resorption, cortical bone porosity, bone fragility, and loss of ex vivo osteogenic differentiation capacity. MicroRNA-29a regulated the abundance of Wnt signaling components (Wnt-3a, glycogen synthase kinase 3β, and β-catenin), the Wnt inhibitor Dkk-1, Akt, and phosphorylated ERK, and the expression of the osteogenic factors RUNX-2 and insulin-like growth factor 1 in bone tissue.
MicroRNA-29a signaling protected against glucocorticoid-induced disturbance of Wnt and Dkk-1 actions and improved osteoblast differentiation and mineral acquisition. Promotion of miR-29a signaling is an alternative strategy for alleviating glucocorticoid-induced bone deterioration.