title: Mechanical loading of the intervertebral disc: from the macroscopic to the cellular level.
abstract: OBJECTIVE
  Mechanical loading represents an integral part of intervertebral disc (IVD) homeostasis. This review aims to summarise recent knowledge on the effects of mechanical loads on the IVD and the disc cells, taking into consideration the changes that IVDs undergo during ageing and degeneration, from the macroscopic to the cellular and subcellular level.
  
  
  METHODS
  Non-systematic literature review.
  
  
  RESULTS
  Several scientific papers investigated the external loads that act on the spine and the resulting stresses inside the IVD, which contribute to estimate the mechanical stimuli that influence the cells that are embedded within the disc matrix. As disc cell responses are also influenced by their biochemical environment, recent papers addressed the role that degradation pathways play in the regulation of (1) cell viability, proliferation and differentiation and (2) matrix production and turnover. Special emphasis was put on the intracellular-signalling pathways, as mechanotransduction pathways play an important role in the maintenance of normal disc metabolism and in disc degenerative pathways.
  
  
  CONCLUSIONS
  Disc cells are exposed to a wide range of mechanical loads, and the biochemical environment influences their responses. Degeneration-associated alterations of the disc matrix change the biochemical environment of disc cells and also the mechanical properties of the disc matrix. Recent studies indicate that these factors interact and regulate disc matrix turnover.
authors.affiliation: Center of Musculoskeletal Research Ulm, Institute of Orthopedic Research and Biomechanics, University of Ulm, Helmholtzstrasse 14, 89081, Ulm, Germany, cornelia.neidlinger-wilke@uni-ulm.de.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Neidlinger-Wilke
authors.forename: Fabio
authors.initials: F
authors.lastname: Galbusera
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.forename: Eleni
authors.initials: E
authors.lastname: Mavrogonatou
authors.forename: Antje
authors.initials: A
authors.lastname: Mietsch
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Wilke
mesh_terms: D000375:Aging; D000818:Animals; D018929:Cell Culture Techniques; D006801:Humans; D007403:Intervertebral Disc / Q000502:physiology*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology; D040542:Mechanotransduction, Cellular; D023421:Models, Animal