title: MiR-26a Rescues Bone Regeneration Deficiency of Mesenchymal Stem Cells Derived From Osteoporotic Mice.
abstract: Osteoporosis, caused by a relative increase of bone resorption over bone formation, is characterized by decreased bone mass and bone strength, resulting in an increased incidence of bone fractures, which often leads to further disability and early mortality in the elderly due to impaired bone healing ability. The majority of therapeutics currently used in clinics for the treatment of osteoporosis are antiresorptive agents that exert their clinical effect by decreasing the rate of bone resorption. However, strategies solely aimed at antiresorption have limited therapeutic efficacy in restoring bone remodeling balance and enhancing osteoporotic fracture healing. Here, we report that miR-26a plays a critical role in modulating bone formation during osteoporosis. We found that miR-26a treatment could effectively improve the osteogenic differentiation capability of mesenchymal stem cells isolated from littermate-derived ovariectomized osteoporotic mice both in vitro and in vivo. MiR-26a exerts its effect by directly targeting Tob1, the negative regulator of BMP/Smad signaling pathway by binding to the 3'-untranslated region and thus repressing Tob1 protein expression. Our findings indicate that miR-26a may be a promising therapeutic candidate to enhance bone formation in treatment of osteoporosis and to promote bone regeneration in osteoporotic fracture healing.
authors.affiliation: Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China; Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China; Department of Oral and Maxillofacial Surgery, Cangzhou Center Hospital, Hebei, P.R. China.
authors.forename: Longkun
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China; Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Liao
authors.affiliation: Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China; Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China. Electronic address: jhchen@fmmu.edu.cn.
authors.forename: Jihua
authors.initials: J
authors.lastname: Chen
authors.affiliation: Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China; Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Shaanxi, P.R. China. Electronic address: yanjin@fmmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001861:Bone Regeneration; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D010012:Osteogenesis; D010024:Osteoporosis / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014162:Transfection; D055114:X-Ray Microtomography
chemical_list: D020413:3' Untranslated Regions; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D051785:Smad Proteins; C490903:Tob1 protein, mouse