title: Loss of Rictor with aging in osteoblasts promotes age-related bone loss.
abstract: Osteoblast dysfunction is a major cause of age-related bone loss, but the mechanisms underlying changes in osteoblast function with aging are poorly understood. This study demonstrates that osteoblasts in aged mice exhibit markedly impaired adhesion to the bone formation surface and reduced mineralization in vivo and in vitro. Rictor, a specific component of the mechanistic target of rapamycin complex 2 (mTORC2) that controls cytoskeletal organization and cell survival, is downregulated with aging in osteoblasts. Mechanistically, we found that an increased level of reactive oxygen species with aging stimulates the expression of miR-218, which directly targets Rictor and reduces osteoblast bone surface adhesion and survival, resulting in a decreased number of functional osteoblasts and accelerated bone loss in aged mice. Our findings reveal a novel functional pathway important for age-related bone loss and support for miR-218 and Rictor as potential targets for therapeutic intervention for age-related osteoporosis treatment.
authors.affiliation: Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.|State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Pinling
authors.initials: P
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.|Department of Biochemistry, Institute of Genetic Engineering, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qiancheng
authors.initials: Q
authors.lastname: Song
authors.affiliation: Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Sichi
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Spine Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Mangmang
authors.initials: M
authors.lastname: Li
authors.affiliation: Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Deng
authors.affiliation: Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
authors.forename: Daozhang
authors.initials: D
authors.lastname: Cai
authors.affiliation: Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
authors.forename: Dadi
authors.initials: D
authors.lastname: Jin
authors.affiliation: Department of Biochemistry, Institute of Genetic Engineering, Southern Medical University, Guangzhou 510515, China.
authors.forename: Anling
authors.initials: A
authors.lastname: Liu
authors.affiliation: Academy of Orthopedics in Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.|State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Bai
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002113:Calcification, Physiologic / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D016166:Free Radical Scavengers / Q000378:metabolism; D017353:Gene Deletion; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology*; D010012:Osteogenesis / Q000235:genetics; D010024:Osteoporosis / Q000378:metabolism* / Q000473:pathology*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016166:Free Radical Scavengers; C547684:MIRN218 microRNA, mouse; D035683:MicroRNAs; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D017382:Reactive Oxygen Species; C525637:rictor protein, mouse