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
AU - Travascio, Francesco
AU - Elmasry, Shady
AU - de Rivero Vaccari, Juan Pablo
N1 - Funding Information:
This study was supported by funds donated to the Biomechanics Research Group of the University of Miami .
PY - 2015/1/21
Y1 - 2015/1/21
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 -