MicroRNA-195-5p Regulates Osteogenic Differentiation of Periodontal Ligament Cells Under Mechanical Loading.
Osteogenic differentiation and bone formation are tightly regulated by several factors, including microRNAs (miRNAs). However, miRNA expression patterns and function during mechanical loading-induced osteogenic differentiation of human periodontal ligament cells (PDLCs) remain unclear. Here, we investigated the differential expression of miRNA-195-5p in the periodontal tissues of mice under orthodontic mechanical loading and in primary human PDLCs exposed to a simulated tension strain. The miR-195-5p was observed to be down-regulated and negatively correlated with osteogenic differentiation. Overexpression of miR-195-5p significantly inhibited PDLC differentiation under cyclic tension strain (CTS), whereas the functional inhibition of miR-195-5p yielded an opposite effect. Further experiments confirmed that WNT family member 3A (WNT3A), fibroblast growth factor 2 (FGF2), and bone morphogenetic protein receptor-1A (BMPR1A), proteins important for osteogenic activity and stability, were direct targets of miR-195-5p. Mechanical loading increased the WNT3A, FGF2, and BMPR1A protein levels, while miR-195-5p inhibited WNT3A, FGF2, and BMPR1A protein expression. WNT, FGF, and BMP signaling were involved in osteogenic differentiation of PDLCs under CTS. Further study confirmed that reintroduction of WNT3A and BMPR1A can rescue the inhibition of miR-195-5p on osteogenic differentiation of PDLCs. Our findings are the first to demonstrate that miR-195-5p is a mechanosensitive gene that plays an important role in mechanical loading-induced osteogenic differentiation and bone formation.
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Maolin
http://orcid.org/0000-0003-4279-3304
M
Chang
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.|Department of Orthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Heng
H
Lin
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.|Department of Orthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Haidi
H
Fu
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.|Department of Orthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Beike
B
Wang
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.|Department of Orthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Guangli
G
Han
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Mingwen
M
Fan
D020413:3' Untranslated Regions; D000293:Adolescent; D000818:Animals; D001665:Binding Sites; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D009967:Orthodontic Appliances; D010012:Osteogenesis; D010513:Periodontal Ligament / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D013997:Time Factors; D014162:Transfection; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D020413:3' Untranslated Regions; C552722:MIRN195 microRNA, human; C569389:MIRN195a microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D016222:Fibroblast Growth Factor 2; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I
bone formation; mechanical loading; miRNAs; periodontal ligament