Such acute effects in response to mechanical loading may be mediated via integrin-FAK, Ca2+-mediated signaling, Vps34 and/or PLD.
We previously showed that the stretch-activated (SA) ion channels and the integrins mediate mechanical loading induced calcium signaling and regulate anabolic and catabolic pathways in chondrocytes [ 3, 28, 55, 56].
These results show that mechanical stress, IL-1β and extracellular visfatin/NAMPT, all stimulated the expression and release of NGF by chondrocytes and thus suggest that the overexpression of visfatin/NAMPT and IL-1β in the OA joint and the increased mechanical loading of cartilage may mediate OA pain via the stimulation of NGF expression and release by chondrocytes.
In contrast, active transport mediated by mechanical loading of porous media is a non-intuitive mechanism that has only been predicted recently from theory, but not yet observed experimentally.
Other potential mechanisms include cumulative mechanical loading and micro-trauma and proprioceptive deficits.
Thus, active solute transport in porous media can indeed be mediated by cyclical mechanical loading.
The evidence shows that normally quiescent chondrocytes, as well as synovial cells, respond to repetitive excess mechanical loading via stress-induced intracellular signals that mediate the production of proinflammatory mediators such as cytokines and cartilage-degrading proteinases [ 33].
Our rationale was that the use of heterozygous conditional IGF-I KO mice with a single copy of the IGF-I gene depleted in osteoblasts and partial ovariectomized mice with a deletion of one ovary will provide a sensitive means to evaluate the interaction between IGF-I and estrogen signaling pathways in mediating the biological response to mechanical loading.
Although insulin-like growth factor-I (IGF-I) and estrogen signaling pathways have been shown to be involved in mediating the bone anabolic response to mechanical loading, it is not known whether these two signaling pathways crosstalk with each other in producing a skeletal response to mechanical loading.
A direct upregulation of the BNP gene by lipopolysaccharide, not mediated by other cytokines and independent from mechanical loading in endotoxemia, has recently been described in rats [ 104].
In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading.
