title: Integrin αv in the mechanical response of osteoblast lineage cells.
abstract: Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src-JNK-YAP/TAZ pathway in response to mechanical stimulation.
authors.affiliation: Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Medical Work-Life-Balance Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Naoe
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Lacy-Hulbert
authors.affiliation: Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan. Electronic address: kikeda@ncgg.go.jp.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D019070:Cell Lineage; D002478:Cells, Cultured; D039564:Integrin alphaV / Q000235:genetics / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D033081:Shear Strength / Q000502:physiology*; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D039564:Integrin alphaV; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D000217:Acyltransferases; C486363:tafazzin protein, mouse; D019061:src-Family Kinases; D048670:MAP Kinase Kinase 4
keywords: Integrin αv; Mechanotransduction; Osteoblast; YAP/TAZ; p130Cas
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