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Open AccessArticle

MicroRNA-29a Counteracts Glucocorticoid Induction of Bone Loss through Repressing TNFSF13b Modulation of Osteoclastogenesis

1
Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
2
Core Laboratory for Phenomics and Diagnostic, Kaohisung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
3
Department of Medical Research, Kaohisung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
4
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(20), 5141; https://doi.org/10.3390/ijms20205141
Received: 12 September 2019 / Revised: 8 October 2019 / Accepted: 14 October 2019 / Published: 17 October 2019
(This article belongs to the Special Issue Secondary Osteoporosis in Adults)
Glucocorticoid excess escalates osteoclastic resorption, accelerating bone mass loss and microarchitecture damage, which ramps up osteoporosis development. MicroRNA-29a (miR-29a) regulates osteoblast and chondrocyte function; however, the action of miR-29a to osteoclastic activity in the glucocorticoid-induced osteoporotic bone remains elusive. In this study, we showed that transgenic mice overexpressing an miR-29a precursor driven by phosphoglycerate kinase exhibited a minor response to glucocorticoid-mediated bone mineral density loss, cortical bone porosity and overproduction of serum resorption markers C-teleopeptide of type I collagen and tartrate-resistant acid phosphatase 5b levels. miR-29a overexpression compromised trabecular bone erosion and excessive osteoclast number histopathology in glucocorticoid-treated skeletal tissue. Ex vivo, the glucocorticoid-provoked osteoblast formation and osteoclastogenic markers (NFATc1, MMP9, V-ATPase, carbonic anhydrase II and cathepsin K) along with F-actin ring development and pit formation of primary bone-marrow macrophages were downregulated in miR-29a transgenic mice. Mechanistically, tumor necrosis factor superfamily member 13b (TNFSF13b) participated in the glucocorticoid-induced osteoclast formation. miR-29a decreased the suppressor of cytokine signaling 2 (SOCS2) enrichment in the TNFSF13b promoter and downregulated the cytokine production. In vitro, forced miR-29a expression and SOCS2 knockdown attenuated the glucocorticoid-induced TNFSF13b expression in osteoblasts. miR-29a wards off glucocorticoid-mediated excessive bone resorption by repressing the TNFSF13b modulation of osteoclastic activity. This study sheds new light onto the immune-regulatory actions of miR-29a protection against glucocorticoid-mediated osteoporosis. View Full-Text
Keywords: miR-29a; osteoclasts; bone loss; TNFSF13b miR-29a; osteoclasts; bone loss; TNFSF13b
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MDPI and ACS Style

Wu, R.-W.; Lian, W.-S.; Chen, Y.-S.; Kuo, C.-W.; Ke, H.-C.; Hsieh, C.-K.; Wang, S.-Y.; Ko, J.-Y.; Wang, F.-S. MicroRNA-29a Counteracts Glucocorticoid Induction of Bone Loss through Repressing TNFSF13b Modulation of Osteoclastogenesis. Int. J. Mol. Sci. 2019, 20, 5141. https://doi.org/10.3390/ijms20205141

AMA Style

Wu R-W, Lian W-S, Chen Y-S, Kuo C-W, Ke H-C, Hsieh C-K, Wang S-Y, Ko J-Y, Wang F-S. MicroRNA-29a Counteracts Glucocorticoid Induction of Bone Loss through Repressing TNFSF13b Modulation of Osteoclastogenesis. International Journal of Molecular Sciences. 2019; 20(20):5141. https://doi.org/10.3390/ijms20205141

Chicago/Turabian Style

Wu, Re-Wen; Lian, Wei-Shiung; Chen, Yu-Shan; Kuo, Chung-Wen; Ke, Huei-Ching; Hsieh, Chin-Kuei; Wang, Shao-Yu; Ko, Jih-Yang; Wang, Feng-Sheng. 2019. "MicroRNA-29a Counteracts Glucocorticoid Induction of Bone Loss through Repressing TNFSF13b Modulation of Osteoclastogenesis" Int. J. Mol. Sci. 20, no. 20: 5141. https://doi.org/10.3390/ijms20205141

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