A computational analysis on the implications of age-related changes in the expression of cellular signals on the role of IGF-1 in intervertebral disc homeostasis

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Insulin-like growth factor-1 (IGF-1) is a well-known anabolic agent in intervertebral discs (IVD), promoting both proteoglycan (PG) biosynthesis and cell proliferation. Accordingly, it is believed that IGF-1 plays a central role in IVD homeostasis. The IGF-mediated anabolic activity in IVD occurs when the growth factor, free from binding proteins (IGFBP), binds to IGF cell surface receptors (IGF-1R). Previous studies reported that, with aging, cellular expression of IGFBP increases, while that of IGF-1R decreases. Both changes in cellular signals are thought to be among the factors that are responsible for the age-related decline in IGF-mediated PG biosynthesis, which ultimately leads to disc degeneration.In this study, a computational model describing the role of IGF-1 in the homeostasis of IVD was deployed in a parametric analysis to investigate the effects of age-related changes in expression of IGF-1R and IGFBP on the IGF-mediated upregulation of PG biosynthesis and cellular proliferation.It was found that changes in the expression of IGF-1R and IGFBP mostly affected the nucleus pulposus, while in the most external disc regions (annulus fibrosus and cartilage endplates) the IVD homeostatic balance was unaltered. It was shown that a decrease of IGF-1R expression caused reduction of both PG levels and cell density in the tissue. In contrast, increase in IGFBP expression increased both PG and cell concentration, suggesting that such change in cellular signaling may be a plausible defense mechanism from age-related IVD degeneration.

Original languageEnglish
Pages (from-to)332-339
Number of pages8
JournalJournal of Biomechanics
Volume48
Issue number2
DOIs
StatePublished - Jan 1 2015

Fingerprint

Insulin-Like Growth Factor Binding Proteins
Intervertebral Disc
Insulin
Somatomedins
Proteoglycans
Homeostasis
Biosynthesis
Intervertebral Disc Degeneration
Cell Proliferation
Cell signaling
Anabolic Agents
Cell Aging
Age Factors
Cell proliferation
Cartilage
Cell Surface Receptors
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Up-Regulation
Cell Count

Keywords

  • Aging
  • IGF-1
  • IGF-1-cell surface receptor
  • IGFBP
  • Intervertebral disc degeneration
  • Intervertebral disc homeostasis

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Rehabilitation
  • Biophysics
  • Biomedical Engineering

Cite this

@article{32f5764033794359a6caa28ad3c144a4,
title = "A computational analysis on the implications of age-related changes in the expression of cellular signals on the role of IGF-1 in intervertebral disc homeostasis",
abstract = "Insulin-like growth factor-1 (IGF-1) is a well-known anabolic agent in intervertebral discs (IVD), promoting both proteoglycan (PG) biosynthesis and cell proliferation. Accordingly, it is believed that IGF-1 plays a central role in IVD homeostasis. The IGF-mediated anabolic activity in IVD occurs when the growth factor, free from binding proteins (IGFBP), binds to IGF cell surface receptors (IGF-1R). Previous studies reported that, with aging, cellular expression of IGFBP increases, while that of IGF-1R decreases. Both changes in cellular signals are thought to be among the factors that are responsible for the age-related decline in IGF-mediated PG biosynthesis, which ultimately leads to disc degeneration.In this study, a computational model describing the role of IGF-1 in the homeostasis of IVD was deployed in a parametric analysis to investigate the effects of age-related changes in expression of IGF-1R and IGFBP on the IGF-mediated upregulation of PG biosynthesis and cellular proliferation.It was found that changes in the expression of IGF-1R and IGFBP mostly affected the nucleus pulposus, while in the most external disc regions (annulus fibrosus and cartilage endplates) the IVD homeostatic balance was unaltered. It was shown that a decrease of IGF-1R expression caused reduction of both PG levels and cell density in the tissue. In contrast, increase in IGFBP expression increased both PG and cell concentration, suggesting that such change in cellular signaling may be a plausible defense mechanism from age-related IVD degeneration.",
keywords = "Aging, IGF-1, IGF-1-cell surface receptor, IGFBP, Intervertebral disc degeneration, Intervertebral disc homeostasis",
author = "Asfour, {Shihab S} and Francesco Travascio and Shady Elmasry and {de Rivero Vaccari}, {Juan Pablo P}",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.jbiomech.2014.11.021",
language = "English",
volume = "48",
pages = "332--339",
journal = "Journal of Biomechanics",
issn = "0021-9290",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - A computational analysis on the implications of age-related changes in the expression of cellular signals on the role of IGF-1 in intervertebral disc homeostasis

AU - Asfour, Shihab S

AU - Travascio, Francesco

AU - Elmasry, Shady

AU - de Rivero Vaccari, Juan Pablo P

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Insulin-like growth factor-1 (IGF-1) is a well-known anabolic agent in intervertebral discs (IVD), promoting both proteoglycan (PG) biosynthesis and cell proliferation. Accordingly, it is believed that IGF-1 plays a central role in IVD homeostasis. The IGF-mediated anabolic activity in IVD occurs when the growth factor, free from binding proteins (IGFBP), binds to IGF cell surface receptors (IGF-1R). Previous studies reported that, with aging, cellular expression of IGFBP increases, while that of IGF-1R decreases. Both changes in cellular signals are thought to be among the factors that are responsible for the age-related decline in IGF-mediated PG biosynthesis, which ultimately leads to disc degeneration.In this study, a computational model describing the role of IGF-1 in the homeostasis of IVD was deployed in a parametric analysis to investigate the effects of age-related changes in expression of IGF-1R and IGFBP on the IGF-mediated upregulation of PG biosynthesis and cellular proliferation.It was found that changes in the expression of IGF-1R and IGFBP mostly affected the nucleus pulposus, while in the most external disc regions (annulus fibrosus and cartilage endplates) the IVD homeostatic balance was unaltered. It was shown that a decrease of IGF-1R expression caused reduction of both PG levels and cell density in the tissue. In contrast, increase in IGFBP expression increased both PG and cell concentration, suggesting that such change in cellular signaling may be a plausible defense mechanism from age-related IVD degeneration.

AB - Insulin-like growth factor-1 (IGF-1) is a well-known anabolic agent in intervertebral discs (IVD), promoting both proteoglycan (PG) biosynthesis and cell proliferation. Accordingly, it is believed that IGF-1 plays a central role in IVD homeostasis. The IGF-mediated anabolic activity in IVD occurs when the growth factor, free from binding proteins (IGFBP), binds to IGF cell surface receptors (IGF-1R). Previous studies reported that, with aging, cellular expression of IGFBP increases, while that of IGF-1R decreases. Both changes in cellular signals are thought to be among the factors that are responsible for the age-related decline in IGF-mediated PG biosynthesis, which ultimately leads to disc degeneration.In this study, a computational model describing the role of IGF-1 in the homeostasis of IVD was deployed in a parametric analysis to investigate the effects of age-related changes in expression of IGF-1R and IGFBP on the IGF-mediated upregulation of PG biosynthesis and cellular proliferation.It was found that changes in the expression of IGF-1R and IGFBP mostly affected the nucleus pulposus, while in the most external disc regions (annulus fibrosus and cartilage endplates) the IVD homeostatic balance was unaltered. It was shown that a decrease of IGF-1R expression caused reduction of both PG levels and cell density in the tissue. In contrast, increase in IGFBP expression increased both PG and cell concentration, suggesting that such change in cellular signaling may be a plausible defense mechanism from age-related IVD degeneration.

KW - Aging

KW - IGF-1

KW - IGF-1-cell surface receptor

KW - IGFBP

KW - Intervertebral disc degeneration

KW - Intervertebral disc homeostasis

UR - http://www.scopus.com/inward/record.url?scp=84920116900&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84920116900&partnerID=8YFLogxK

U2 - 10.1016/j.jbiomech.2014.11.021

DO - 10.1016/j.jbiomech.2014.11.021

M3 - Article

C2 - 25488135

AN - SCOPUS:84920116900

VL - 48

SP - 332

EP - 339

JO - Journal of Biomechanics

JF - Journal of Biomechanics

SN - 0021-9290

IS - 2

ER -