Osteoporosis International

, Volume 19, Issue 9, pp 1237–1246

Integrins, insulin like growth factors, and the skeletal response to load

Special Feature

DOI: 10.1007/s00198-008-0597-z

Cite this article as:
Bikle, D.D. Osteoporos Int (2008) 19: 1237. doi:10.1007/s00198-008-0597-z

Abstract

Bone loss during skeletal unloading, whether due to neurotrauma resulting in paralysis or prolonged immobilization due to a variety of medical illnesses, accelerates bone loss. In this review the evidence that skeletal unloading leads to bone loss, at least in part, due to disrupted insulin like growth factor (IGF) signaling, resulting in reduced osteoblast proliferation and differentiation, will be examined. The mechanism underlying this disruption in IGF signaling appears to involve integrins, the expression of which is reduced during skeletal unloading. Integrins play an important, albeit not well defined, role in facilitating signaling not only by IGF but also by other growth factors. However, the interaction between selected integrins such as αυβ3 and β1 integrins and the IGF receptor are of especial importance with respect to the ability of bone to respond to mechanical load. Disruption of this interaction blocks IGF signaling and results in bone loss.

Keywords

Bone IGF Integrin Mechanical load Osteoblast Osteoclast 

Abbreviations

BMSC

Bone marrow stromal cells

FAK

Focal adhesion kinase

grb2

Growth receptor binding protein-2

GEF

Guanine nucleotide exchange factor

IGF-R

Insulin like growth factor (IGF) and its receptor

IRS

Insulin receptor substrate

MAPK

Mitogen activated protein kinase

NO

Nitric oxide

PI3K

Phosphatidyl inositol 3 kinase

PIP2 and PIP3

Phosphatidyl inositol bis- and tris-phosphate

PDK

Phosphoinositide dependent kinase

PTB

Phosphotyrosine binding protein

Pyk

Phosphotyrosine kinase

PGE2

Prostaglandin E2

PKB/Akt

Protein kinase B

SOS

Son of sevenless

SH2

src homology 2

SHPS

SH2 domain containing protein tyrosine phosphatase (SHP) and its substrate

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  1. 1.Medicine and DermatologyUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Special Diagnostic and Treatment CenterVeterans Affairs Medical CenterSan FranciscoUSA

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