Mechanics and biology in intervertebral disc degeneration: a vicious circle  P.-P.A. Vergroesen, I. Kingma, K.S. Emanuel, R.J.W. Hoogendoorn, T.J. Welting, B.J. van Royen, J.H. van Dieën, T.H. Smit  Osteoarthritis and Cartilage  Volume 23, Issue 7, Pages 1057-1070 (July 2015) DOI: 10.1016/j.joca.2015.03.028 Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Concept of the degenerative circle of intervertebral disc degeneration. Osteoarthritis and Cartilage 2015 23, 1057-1070DOI: (10.1016/j.joca.2015.03.028) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 The degenerative circle of intervertebral disc degeneration. Homeostasis of the intervertebral disc is dependent on the interaction of cells, extracellular matrix and biomechanical stress. If this balance is disturbed, the cells stop producing proteoglycans, this will give a reduction in hydrostatic pressure and increase shear forces on the cells. An increase of shear forces further decreases the production of proteoglycans, leading to progressive degeneration. Osteoarthritis and Cartilage 2015 23, 1057-1070DOI: (10.1016/j.joca.2015.03.028) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 The efficacy of animal models applied to the degenerative circle. Intervertebral disc degeneration can be induced through any of the three main elements of the degenerative circle, which further indicates a positive feedback loop. Osteoarthritis and Cartilage 2015 23, 1057-1070DOI: (10.1016/j.joca.2015.03.028) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Additions to the degenerative circle. The degenerative circle is not a final account of intervertebral disc degeneration, possible future additions to the model are included. It is also important to notice that the degenerative circle is drawn upon an individual's genetic background, which probably influences all pathways included in the model. Osteoarthritis and Cartilage 2015 23, 1057-1070DOI: (10.1016/j.joca.2015.03.028) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions