Integrin αv in the mechanical response of osteoblast lineage cells

Journal Article · Fri May 02 04:00:00 EDT 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2014.04.006· OSTI ID:22416417

Kaneko, Keiko ^[1]; Ito, Masako ^[2]; Naoe, Yoshinori ^[3]; Lacy-Hulbert, Adam ^[4]; Ikeda, Kyoji ^[1]

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1. Department of Bone and Joint Disease, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511 (Japan)
2. Medical Work-Life-Balance Center, Nagasaki University Hospital, Nagasaki 852-8501 (Japan)
3. Department of Mechanism of Aging, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511 (Japan)
4. Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114 (United States)

Highlights: • Deletion of integrin αv in osteoblast lineage results in an impaired SOST response to loading in vivo. • c-Src–p130Cas–JNK–YAP/TAZ is activated via integrin αv on osteoblasts in response to FSS. • Deletion of integrin αv in osteoblasts results in impaired responses to mechanical stimulation. • Integrin αv is a key component of the mechanosensing machinery in bone. - 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.

• OSTI ID: 22416417
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 447; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BONE CELLS
FLUIDS
GENES
IN VIVO
INHIBITION
LOADING
PHOSPHORYLATION
RECEPTORS
SKELETON
STIMULATION
STRESSES
SUBSTRATES
TRANSLOCATION