1. A QUANTITATIVE EVALUATION OF THE ROLE OF CELL SENESCENCE IN INTERVERTEBRAL DISC DEGENERATION
1Elmasry, S; 1Asfour, S; 2J. P. de Rivero Vaccari; +1Travascio, F
1Biomech. Research Lab, Dept. Industrial Eng., Univ. Miami, Coral Gables, FL
2Department of Neurological Surgery University of Miami, Miami, FL
BACKGROUND
the natural process of aging is considered to be one of the primary causes for intervertebral disc degeneration [1]
Insulin-like growth factor-1 (IGF-1) upregulates anabolism in IVD via binding to IGF-1 cell receptors (IGF-1R). At the same time, IGF-1 can reversibly bind to IGF binding proteins (IGFBP) [2]
It has been shown that, in IVD, IGF-1R expression decreases, while endogenous IGFBP production increases with aging [3]
HYPOTHESIS
Age-related changes in both IGFBP and IGF-1R expression may be responsible for the decline in ECM biosynthesis and cellularity, eventually leading to IVD degeneration
OBJECTIVE
To investigate effects of age-related changes of IGF-1R expression and endogenous IGFBP on IVD homeostasis
METHODS
A physicochemical computational model describing IVD homeostasis with aging was deployed [2, 4], see Fig.1
Three hypothetical scenarios of aging: ‘young-adult’, ‘adult’, and ‘elder’, were assumed in our investigation. Expression of IGFBP and IGF-1R changed with age [3]
Fig. 2: Aging affects ECM composition and cell viability in nucleus pulposus. (a) Cell density, (b) PG Content
Fig. 3: IGFBP extends IGF-1 half-life and improves IVD homeostasis. (a) Cell density; (b) PG content. Data normalized with respect to ‘young-adult’ case
RESULTS & DISCUSSION:
In agreement with experimental studies [1], PG concentration in NP and cell density decreased with aging. However, no effects were observed in either AF or CEP (Fig. 2)
IGFBP exerts a beneficial effect on IVD homeostasis by extending IGF-1 half-life, thus increasing growth factor penetration within the disc and resulting in the formation of a larger number of IGF-1/IGF-1R. Accordingly, both PG levels and cellularity increase (Fig. 3)
Data suggest that age-related increase of IGFBP expression might be a plausible mechanism of defense by disc cells against degeneration
REFERENCES
[1]Roughley, Spine, 29:2691-9, 2004, [2]Travascio et al., J Biomech, 47: , 2014, [3]Okuda et al., Spine, 26:2421-6, 2001, [4]Asfour et al., J Biomech, 48:332-9, 2014
ACKNOWLEDGEMENTS: Study supported by funds donated to the Biomechanics Research Group of the University of Miami
Fig. 1: Schematic of the computational model describing IGF-1 and nutrients transport in the disc and their implications on IVD homeostasis