title: The Trk family of neurotrophin receptors is downregulated in the lumbar spines of rats with congenital kyphoscoliosis.
abstract: Congenital scoliosis is a condition characterized by spinal curvature beyond the physiological norm. The molecular mechanisms underlying the pathogenesis of congenital scoliosis are beginning to be clarified; however, the genes related to congenital scoliosis are still unknown. We herein report the results of a comprehensive analysis of gene expression in the spines from a rat model of congenital kyphoscoliosis obtained using DNA microarrays. The rats (Ishibashi rats, IS) showed decreased expression levels of genes associated with bone formation, such as those associated with retinol metabolism and type I collagen. Interestingly, the flexion sites of the IS rats showed low expression levels of tropomyosin receptor kinases (Trks: TrkA, TrkB, and TrkC), which belong to the neurotrophic receptor tyrosine kinase family. Moreover, this phenomenon was observed only in the flexion sites of the spine, and the expression levels of Trks in other parts of the spine in these rats were normal. The decreased expression levels of Trks were observed at both the mRNA and protein levels. We also observed that the number of Trk-immunopositive cells in the lumbar spine in the IS rats was lower than that in wild-type rats. These findings indicate that the Trks have an important function in regulating normal bone formation, and provide a molecular explanation for the pathogenesis of congenital kyphoscoliosis.
authors.affiliation: Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.|Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsunoda
authors.affiliation: Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Haku
authors.initials: H
authors.lastname: Iizuka
authors.affiliation: Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ichinose
authors.affiliation: Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Iizuka
authors.affiliation: Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Tokue
authors.initials: T
authors.lastname: Mieda
authors.affiliation: Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. shimokawa-n@takasaki-u.ac.jp.|Department of Nutrition, Takasaki University of Health and Welfare, 37-1 Nakaorui-machi, Takasaki, Gunma, 371-0033, Japan. shimokawa-n@takasaki-u.ac.jp.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimokawa
authors.affiliation: Department of Orthopedic Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagishi
authors.affiliation: Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koibuchi
mesh_terms: D000818:Animals; D015536:Down-Regulation; D007738:Kyphosis / Q000151:congenital* / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012600:Scoliosis / Q000151:congenital* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D017475:Receptors, Nerve Growth Factor
keywords: Congenital scoliosis; DNA microarrays; Kyphoscoliosis model rats; Trk family neurotrophin receptors