Department of Clinical Sciences of Companion Animals, Utrecht University, Utrecht, The Netherlands.
Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1044-52. doi: 10.1152/ajpendo.00170.2010. Epub 2010 Sep 21.
Disparities in longitudinal growth within a species can be partly explained by endocrinological differences. We hypothesized that regulatory networks acting locally in the growth plate may also be important. We tested this hypothesis by evaluating 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) using immunohistochemistry and quantitative (q)PCR. The rib growth plates of GD were 1.7 times thicker compared with those of MP, with larger proliferative (in absolute 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 qPCR findings showed that the vitamin D pathway was more active in GD than in MP. Staining for 1α- and 24-hydroxylase was more abundant and intense in GD and the gene expressions of 1α-hydroxylase and the vitamin D receptor-driven 24-hydroxylase were six- and eightfold higher in GD vs. MP, respectively. Consistent with the immunohistochemistry findings, the expression of mRNA for components of the parathyroid hormone-related peptide (PTHrP)-IHH loop was different in GD compared with MP, with there being a relative threefold downregulation of Pthrp and a tenfold upregulation of Ihh in GD vs MP. These differences suggest that the effects of IHH in the regulation of chondrocyte proliferation and hypertrophy, both independently of PTHrP, can become more dominant during rapid growth rates. In conclusion, our data suggest that, in addition to modest endocrine differences, more pronounced changes in the expression of locally acting regulatory networks, such as the IGF system, vitamin D pathway, and PTHrP-IHH feedback loop are important contributors to within-species disparities in growth rates.
物种内纵向生长的差异部分可以通过内分泌差异来解释。我们假设，局部作用于生长板的调控网络也可能很重要。我们通过使用免疫组织化学和定量（q）PCR 评估 IGF/IGFBP 表达、维生素 D 途径和 PTHrP-Indian Hedgehog (IHH) 反馈环，来验证这个假设。我们从 10 周龄和 21 周龄的小型（迷你贵宾犬，MP）和大型犬（大丹犬，GD）的肋骨生长板中评估了这一假设。与 MP 相比，GD 的肋骨生长板厚 1.7 倍，增殖（绝对值）和肥大（绝对值和相对值）区较大。生长板的 IGF/IGFBP 基因表达谱显示，igfbp2、-4 和 -6 的基因表达降低，而 IGF-I 和 IGF-II 及其各自的受体在 GD 与 MP 之间的表达不变。免疫组织化学和 qPCR 发现，维生素 D 途径在 GD 中比在 MP 中更活跃。1α-和 24-羟化酶的染色在 GD 中更为丰富和强烈，1α-羟化酶和维生素 D 受体驱动的 24-羟化酶的基因表达在 GD 中分别是 MP 的六倍和八倍。与免疫组织化学结果一致，甲状旁腺激素相关肽（PTHrP）-IHH 环的组成部分的 mRNA 表达在 GD 与 MP 之间存在差异，Pthrp 相对下调三倍，而 Ihh 上调十倍。这些差异表明，在快速生长速率下，IHH 对软骨细胞增殖和肥大的调节作用（独立于 PTHrP）可能更为显著。总之，我们的数据表明，除了适度的内分泌差异外，局部作用的调控网络（如 IGF 系统、维生素 D 途径和 PTHrP-IHH 反馈环）表达的更显著变化，是生长速率种内差异的重要贡献者。
