title: MicroRNA-338-3p inhibits glucocorticoid-induced osteoclast formation through RANKL targeting.
abstract: The differentiation deficiencies of osteoclast precursors (pre-OCs) may contribute to osteoporosis. Research on osteoporosis has recently focused on microRNAs (miRNAs) that play crucial roles in pre-OC differentiation. In the current study, we aimed to analyze the expression and function of the glucocorticoid (GC)-associated miRNA-338-3p (miR-338-3p) in osteoclast formation. We found that dexamethasone induced osteoclast differentiation and inhibited miR-338-3p expression. Overexpression of an miR-338-3p mimic in osteoclast precursor cells attenuated GC-induced osteoclast formation and bone resorption, whereas inhibition of miR-338-3p reversed these effects. The expression of the nuclear factor κB ligand RANKL, a potential target gene of miR-338-3p, was inversely correlated with miR-338-3p expression in pre-OCs. Furthermore, we demonstrated that RANKL was directly regulated by miR-338-3p and re-introduction of RANKL reversed the inhibitory effects of miR-338-3p on osteoclast formation and bone resorption. Taken together, these findings demonstrate that miR-338-3p may play a significant role in GC-induced osteoclast differentiation and function by targeting RANKL in osteoclasts.
authors.affiliation: Department of Physical Therapy, Wuxi Tongren International Rehabilitation Hospital, Wuxi, Jiangsu, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: School of Nursing, Nantong University, Nantong, Jiangsu, China.
authors.forename: G L
authors.initials: GL
authors.lastname: Geng
authors.affiliation: Department of Physical Therapy, Wuxi Tongren International Rehabilitation Hospital, Wuxi, Jiangsu, China larferi@126.com.
authors.forename: B
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Physical Therapy, Wuxi Tongren International Rehabilitation Hospital, Wuxi, Jiangsu, China.
authors.forename: C P
authors.initials: CP
authors.lastname: Liang
authors.affiliation: Department of Physical Therapy, Wuxi Tongren International Rehabilitation Hospital, Wuxi, Jiangsu, China.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Rehabilitation, Wuxi Tongren International Rehabilitation Hospital, Wuxi, Jiangsu, China.
authors.forename: J C
authors.initials: JC
authors.lastname: Bao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005938:Glucocorticoids; D035683:MicroRNAs; C000591274:Mirn338 microRNA, mouse; D020320:Oligoribonucleotides, Antisense; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D003907:Dexamethasone