Intraspecies disparity in growth rate is associated with differences inexpression of local growth plate regulators.

摘要

Disparities in longitudinal growth within a species can be partly explained byendocrinological differences. We hypothesized that regulatory networks actinglocally in the growth plate may also be important. We tested this hypothesis byevaluating the IGF/IGFBP expression, the vitamin D pathway, and the PTHrP-Indian hedgehog (IHH) feedback loop in rib growth plates from 10- and 21-wk-old small-(Miniature Poodles, MP) and large-breed dogs (Great Danes, GD) usingimmunohistochemistry and quantitative (q)PCR. The rib growth plates of GD were1.7 times thicker compared with those of MP, with larger proliferative (inabsolute terms) and larger hypertrophic (in absolute and relative terms) zones.IGF/IGFBP gene expression profiling of the growth plates revealed decreased gene expression of igfbp2, -4, and -6 and an unaltered expression of igf-I and igf-II and their respective receptors in GD vs. MP. Immunohistochemistry and qPCRfindings showed that the vitamin D pathway was more active in GD than in MP.Staining for 1alpha- and 24-hydroxylase was more abundant and intense in GD and thegene expressions of 1alpha-hydroxylase and the vitamin D receptor-driven24-hydroxylase were six- and eightfold higher in GD vs. MP, respectively.Consistent with the immunohistochemistry findings, the expression of mRNA forcomponents of the parathyroid hormone-related peptide (PTHrP)-IHH loop wasdifferent in GD compared with MP, with there being a relative threefolddownregulation of Pthrp and a tenfold upregulation of Ihh in GD vs MP. Thesedifferences suggest that the effects of IHH in the regulation of chondrocyteproliferation and hypertrophy, both independently of PTHrP, can become moredominant during rapid growth rates. In conclusion, our data suggest that, inaddition to modest endocrine differences, more pronounced changes in theexpression of locally acting regulatory networks, such as the IGF system, vitaminD pathway, and PTHrP-IHH feedback loop are important contributors towithin-species dis...