Effects of Mechanical Loading on Intervertebral Disc Metabolism In Vivo

Abstract

The overall goal of this work is to define more clearly which mechanical loading conditions are associated with accelerated disc degeneration. This article briefly reviews recent studies describing the effects of mechanical loading on the metabolism of intervertebral disc cells and defines hypothetical models that provide a framework for quantitative relationships between mechanical loading and disc-cell metabolism. Disc cells respond to mechanical loading in a manner that depends on loading magnitude, frequency, and duration. On the basis of the current data, four models have been proposed to describe the effects of continuous loading on cellular metabolism: (1) on/off response, in which messenger ribonucleic acid (mRNA) transcription remains altered for the duration of loading; (2) maintenance, characterized by an initial change in mRNA levels with return to baseline levels; (3) adaptation, in which mRNA transcription is altered and remains at a new steady state; and (4) no response. In addition, five hypothetical mechanisms that describe the long-term consequences of these metabolic changes on disc-remodeling are presented. The transient nature of gene expression along with enzyme activation/inhibition is associated with changes at the protein level. The hypothetical models presented provide a framework for obtaining quantitative relationships between mechanical loading, gene expression, and changes at the compositional level; however, additional factors, such as regulatory mechanisms, must also be considered when describing disc-remodeling. A more quantitative relationship between mechanical loading effects and the metabolic response of the disc will contribute to injury prevention, facilitate more effective rehabilitation treatments, and help realize the potential of biologic and tissue engineering approaches toward disc repair.

Are animal models useful for studying human disc disorders/degeneration?

“…The variation of properties (biomechanical, morphological and cellular) between regions within the disc itself is also an important factor to consider in choosing and designing the model. For example, the cell types vary with location, with those from the annulus differing not only in morphology but also in their metabolism, response to applied loads, etc., from the cells within the NP [57,70,125,150].…”

Gender differences after lumbar sequestrectomy: a prospective clinical trial using quantitative sensory testing

“…These dissimilarities on the other hand are due to hormonal differences and the onset of menstruation-related pain in women [36]. Nevertheless, disc degeneration is multifaceted, traditionally attributed to age, mechanical loading, gender, trauma, obesity and other factors impairing disc nutrition [37][38][39][40][41].…”

Stress in lumbar intervertebral discs during distraction: a cadaveric study

“…It is possible that the motion or change in stress results in mechanobiological events that lead to pain relief or promote disc health [39,40]. Studies using both animal and in vitro models have demonstrated that mechanical stress may play a role in the regulation of both degradative and anabolic processes in discs [41][42][43].…”