PMID- 28331074
OWN - NLM
STAT- MEDLINE
DCOM- 20171006
LR  - 20181113
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 28
IP  - 10
DP  - 2017 May 15
TI  - Osteopontin inhibits osteoblast responsiveness through the down-regulation of 
      focal adhesion kinase mediated by the induction of low-molecular weight protein 
      tyrosine phosphatase.
PG  - 1326-1336
LID - 10.1091/mbc.E16-10-0716 [doi]
AB  - Osteopontin (OPN) is an osteogenic marker protein. Osteoblast functions are 
      affected by inflammatory cytokines and pathological conditions. OPN is highly 
      expressed in bone lesions such as those in rheumatoid arthritis. However, local 
      regulatory effects of OPN on osteoblasts remain ambiguous. Here we examined how 
      OPN influences osteoblast responses to mechanical stress and growth factors. 
      Expression of NO synthase 1 (Nos1) and Nos2 was increased by low-intensity pulsed 
      ultrasound (LIPUS) in MC3T3-E1 cells and primary osteoblasts. The increase of 
      Nos1/2 expression was abrogated by both exogenous OPN overexpression and 
      recombinant OPN treatment, whereas it was promoted by OPN-specific siRNA and OPN 
      antibody. Moreover, LIPUS-induced phosphorylation of focal adhesion kinase (FAK), 
      a crucial regulator of mechanoresponses, was down-regulated by OPN treatments. 
      OPN also attenuated hepatocyte growth factor-induced vitamin D receptor (Vdr) 
      expression and platelet-derived growth factor-induced cell mobility through the 
      repression of FAK activity. Of note, the expression of low-molecular weight 
      protein tyrosine phosphatase (LMW-PTP), a FAK phosphatase, was increased in both 
      OPN-treated and differentiated osteoblasts. CD44 was a specific OPN receptor for 
      LWW-PTP induction. Consistently, the suppressive influence of OPN on osteoblast 
      responsiveness was abrogated by LMW-PTP knockdown. Taken together, these results 
      reveal novel functions of OPN in osteoblast physiology.
CI  - (c) 2017 Kusuyama et al. This article is distributed by The American Society for 
      Cell Biology under license from the author(s). Two months after publication it is 
      available to the public under an Attribution-Noncommercial-Share Alike 3.0 
      Unported Creative Commons License 
      (http://creativecommons.org/licenses/by-nc-sa/3.0).
FAU - Kusuyama, Joji
AU  - Kusuyama J
AD  - Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima 
      University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, 
      Japan.
FAU - Bandow, Kenjiro
AU  - Bandow K
AD  - Department of Oral Biology and Tissue Engineering, Meikai University School of 
      Dentistry, Sakato 350-0283, Japan.
FAU - Ohnishi, Tomokazu
AU  - Ohnishi T
AD  - Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima 
      University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, 
      Japan.
FAU - Hisadome, Mitsuhiro
AU  - Hisadome M
AD  - Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima 
      University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, 
      Japan.
AD  - Department of Dermatology, Field of Advanced Therapeutics, Kagoshima University 
      Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
FAU - Shima, Kaori
AU  - Shima K
AD  - Department of Oral Pathology, Field of Oncology, Kagoshima University Graduate 
      School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
FAU - Semba, Ichiro
AU  - Semba I
AD  - Department of Oral Pathology, Field of Oncology, Kagoshima University Graduate 
      School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
FAU - Matsuguchi, Tetsuya
AU  - Matsuguchi T
AD  - Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima 
      University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, 
      Japan tmatsugu@dent.kagoshima-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20170322
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 106441-73-0 (Osteopontin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Adhesion
MH  - Cell Differentiation
MH  - Cell Movement
MH  - Down-Regulation
MH  - Focal Adhesion Protein-Tyrosine Kinases/metabolism
MH  - Mice
MH  - Molecular Weight
MH  - Nitric Oxide Synthase/metabolism
MH  - Osteoblasts/*metabolism/physiology
MH  - Osteopontin/*metabolism/physiology
MH  - Phosphorylation
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Protein Tyrosine Phosphatases/*metabolism
MH  - Signal Transduction/drug effects
PMC - PMC5426847
EDAT- 2017/03/24 06:00
MHDA- 2017/10/07 06:00
PMCR- 2017/07/30
CRDT- 2017/03/24 06:00
PHST- 2016/10/13 00:00 [received]
PHST- 2017/03/06 00:00 [revised]
PHST- 2017/03/13 00:00 [accepted]
PHST- 2017/03/24 06:00 [pubmed]
PHST- 2017/10/07 06:00 [medline]
PHST- 2017/03/24 06:00 [entrez]
PHST- 2017/07/30 00:00 [pmc-release]
AID - mbc.E16-10-0716 [pii]
AID - E16-10-0716 [pii]
AID - 10.1091/mbc.E16-10-0716 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2017 May 15;28(10):1326-1336. doi: 10.1091/mbc.E16-10-0716. Epub 
      2017 Mar 22.