The Effect of Calmodulin Antagonists on Experimental Scoliosis

Abstract

The incidence and magnitude of scoliosis in pinealectomized chicken may be decreased by the administration of TMX, presumably because of this drugs' calmodulin antagonism. Further studies on higher animals and dosage and timing are required.

Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model

“…These findings suggest that SERMs such as TMX and RLX may be effective in the reversal of osteopenia and in parallel, the scoliotic deformity in animal models. In other words, the mechanism of action might not be solely calmodulin antagonism, as assumed in previous studies [17,19], but also estrogen receptor modulation. However, there is evidence showing that RLX binds to CaM receptors, although the antagonistic effect has not been confirmed by other studies [36].…”

“…The concept of modification of the natural history of scoliosis using TMX first originated based on the hypothesis that deformity may be caused by an abundance of Calmodulin (CaM), which is a calcium-binding receptor protein that regulates the cAMP-based enzyme systems, thereby the contractile properties of muscle cells by way of regulating the Ca transport through the cellular membrane [29], and also the neurotransmitter that is effective in regulating melatonin release [30]. Therefore, AIS is modeled as a neuromuscular spinal deformity in which the melatonin effect on paraspinal muscle tonus may be by way of calmodulin antagonism, in that the absence of calmodulin antagonism in melatonin deficient scoliosis models may be the consequence of a paraspinal muscle tone imbalance eventually leading to scoliotic curves [17]. In previous studies, TMX as a calmodulin antagonist was used to replace the anticalmodulin effect of melatonin on melatonin deficient scoliotic mice and pinealectomized scoliotic chicken models [17,19].…”

“…Therefore, AIS is modeled as a neuromuscular spinal deformity in which the melatonin effect on paraspinal muscle tonus may be by way of calmodulin antagonism, in that the absence of calmodulin antagonism in melatonin deficient scoliosis models may be the consequence of a paraspinal muscle tone imbalance eventually leading to scoliotic curves [17]. In previous studies, TMX as a calmodulin antagonist was used to replace the anticalmodulin effect of melatonin on melatonin deficient scoliotic mice and pinealectomized scoliotic chicken models [17,19]. Those results demonstrated that TMX did not have an effect on the incidence of scoliosis but decreased the curve progression and even reversed the curve magnitudes in some cases.…”

“…Furthermore, these investigators demonstrated that development of scoliosis could be prevented by the replantation of the pineal gland in skeletal muscle or by the administration of melatonin as a replacement therapy [12], which however, could not be replicated by others [15,16]. In addition to chickens, scoliosis can be produced in pinealectomized rats and a melatonin deficient strain of mice (C57Bl6) as well, provided that they are forced to attain a bipedal posture by amputation of the forelimbs and tails [17,18].…”

“…Research results demonstrated that tamoxifen (TMX), a Selective Estrogen Receptor Modulator (SERM) as well as a Calmodulin (CaM) antagonist, does not prevent the occurrence of the scoliotic deformities in either the pinealectomized chicken or melatonin deficient mice models; but decreases the rate of progression of deformity in both [17,19]. In addition, TMX may induce a reversal of the curves in significantly higher number of animals compared to controls.…”