European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2023
Calcium sensing and signaling are impaired in the lumbar spine of a rat model of congenital kyphosis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Takahashi Itsuki, Watanabe Yusuke, Sonoda Hiroyuki, Tsunoda Daisuke, Amano Izuki, Koibuchi Noriyuki, Iizuka Haku, Shimokawa Noriaki
Аннотация
PURPOSE: Kyphosis involves spines curving excessively backward beyond their physiological curvature. Although the normal structure of the spinal vertebrae is extremely important for maintaining posture and the normal function of the thoracic and abdominal organs, our knowledge concerning the pathogenesis of the disease is insufficient. We herein report that the downregulation of the calcium signaling pathway is involved in the pathogenesis of congenital kyphosis.
METHODS: The third to fifth lumbar spine segments, the kyphotic region of Ishibashi (IS) rats, which are used as a model of congenital kyphoscoliosis, were collected. A DNA microarray, quantitative PCR, Western blotting, and immunohistochemistry were used to measure the expression of genes and proteins related to intracellular calcium signaling.
RESULTS: We found that the expression of calcium-sensing receptor (CaSR) and transient receptor potential vanilloid 1 (Trpv1)-two receptors involved in the calcium signaling-was decreased in the lumbar spine of IS rats. We also observed that the number of CaSR-immunoreactive and Trpv1-immunoreactive cells in the lumbar spine of IS rats was lower than in wild-type rats. Furthermore, the expression of intracellular molecules downstream of these receptors, such as phosphorylated protein kinase C, c-Jun N-terminal kinase, and neural EGFL-like 1, was also reduced. In fact, the calcium content in the lumbar spine of IS rats was significantly lower than that in wild-type rats.
CONCLUSION: These results indicate that adequate calcium signaling is extremely important for the regulation of normal bone formation and may also be a key factor for understanding the pathogenesis of congenital kyphosis.
METHODS: The third to fifth lumbar spine segments, the kyphotic region of Ishibashi (IS) rats, which are used as a model of congenital kyphoscoliosis, were collected. A DNA microarray, quantitative PCR, Western blotting, and immunohistochemistry were used to measure the expression of genes and proteins related to intracellular calcium signaling.
RESULTS: We found that the expression of calcium-sensing receptor (CaSR) and transient receptor potential vanilloid 1 (Trpv1)-two receptors involved in the calcium signaling-was decreased in the lumbar spine of IS rats. We also observed that the number of CaSR-immunoreactive and Trpv1-immunoreactive cells in the lumbar spine of IS rats was lower than in wild-type rats. Furthermore, the expression of intracellular molecules downstream of these receptors, such as phosphorylated protein kinase C, c-Jun N-terminal kinase, and neural EGFL-like 1, was also reduced. In fact, the calcium content in the lumbar spine of IS rats was significantly lower than that in wild-type rats.
CONCLUSION: These results indicate that adequate calcium signaling is extremely important for the regulation of normal bone formation and may also be a key factor for understanding the pathogenesis of congenital kyphosis.