Originally posted by structural75
Excerpt taken from:
Scoliosis. 2006; 1: 16.
Published online 2006 October 18. doi: 10.1186/1748-7161-1-16.
Copyright © 2006 Stokes et al; licensee BioMed Central Ltd.
Biomechanical spinal growth modulation and progressive adolescent scoliosis –a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE
Ian AF Stokes,1 R Geoffrey Burwell,2 and Peter H Dangerfield3
1Department of Orthopaedics and Rehabilitation, University of Vermont, Burlington, Vermont 05405, USA
2The Centre for Spinal Studies & Surgery, Queen's Medical Centre, Nottingham, NG7 2UH, UK
3Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK
Mechanotransduction in articular cartilage, vertebral growth plates and other tissues and organs
Comment no. 43
Mechanotransduction is the process by which cells convert mechanical energy into electrical or chemical signals [72,73,75]. It lies within the field of mechanobiology that in the skeleton includes the three effects of Hueter-Volkmann, Pauwels and Wolff [85,132-134]. (The Pauwels' effect is where intermittent pressure within the limits of physiological stress and strain stimulates the growth plates of a healthy bone [2,7]). In addition to studies on the intervertebral disc [162,163] there is much recent study of articular cartilage as efforts expand to discover disease-modifying drugs to treat or prevent osteoarthritis [164-167]. According to Ingber [73] mechanical signals may be integrated with other environmental signals – including growth factors and extracellular matrix – and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics. Stoltz [168] states that in chondrocytes many genes are regulated up and down by mechanical forces and the response depends not only on the duration and amplitude of the forces, but also on their variations in time. Lammi [169] reviewing articular cartilage states that possible mechanotransduction pathways in chondrocytes activated by load include the integrin-interleukin-4 route, NMDA receptors, and P2Y2 purinoceptors the latter involving ATP [170]. If such load-sensitive receptors are present in chondrocytes of endplate physes variation in gene expression by age, gender and topography may underlie the vulnerability to curve progression under eccentric load. There is preliminary work evaluating the effect of mechanical loads on mRNA expression of rat tibial growth plate cells [20]. Are any of the current methods now being used to study articular cartilage mechanotransduction being applied to endplates?
Response
The mechanical influences on articular chondrocytes and extra-cellular matrix synthesis and degradation are reviewed in Grodzinsky et al [171]. However, I suspect that little of this information can be applied to the very different growth plate chondrocytic phenotype characterized by high rates of proliferation (cycle time about 48 hours), rapid hypertrophy and abundant matrix synthesis, and eventual apoptosis. The mechanisms of mechanotransduction and their effects on cells in each stage of this differentiation cascade (and the rate of differentiation itself) are probably very specific to growth plate chondrocytes.
Moderator: In addition to skeletal tissues, muscles, tendons and ligaments [78,79], mechanotransduction is involved in the senses of touch, balance (spindle receptors and proprioceptors), hearing, baroreceptors (blood pressure), vascular remodeling from fluid shear stress [172] and systemic osmolarity [74]. Little is known about how mechanical input forces delivered to a cell result in a repertoire of output physiologic responses [74,75,172] though recently force-transducing molecules – mechanosensitive ion channels – have been identified in cell membranes with lipids [74] and calcium channels in osteoblasts [173] intimately involved. In certain connective tissues mechanotransduction appears to involve cyclical mechanical strain upregulating extracellular matrix genes suggesting that such genes are possible targets for novel therapeutic intervention [81].
Comment