Background: With the improvements in living standards, height is getting more attention. Malnutrition is one of the main causes of children's short stature; therefore, nutritional intervention in adolescence is the key to prevent short stature. The peptides from Antarctic Krill (AKPs), the ideal protein model, act in bone formation and anti-osteoporosis. However, the studies on promoting longitudinal bone growth by AKPs have not been reported.

Methods: Three-week-old male ICR mice, to construct the adolescent mice model, randomly divided into three groups: normal group, casein group (casein, 300 mg/kg·BW), and AKPs group (AKPs, 300 mg/kg·BW). After 21 days of drug administration, the effects of AKPs on serum biochemical indexes and femur histomorphology of mice, and the mechanism of AKPs promoting longitudinal bone growth was discussed.

Results: AKPs significantly increased longitudinal bone growth and improved bone strength. In addition, AKPs remarkably promoted proliferation and hypertrophy of chondrocytes in the growth plate. The further mechanism revealed that AKPs increased serum Growth Hormone (GH) and Insulin-Like Growth Factors-1(IGF-1) contents, which activated the downstream GH/IGF-1 axis signaling pathways. Moreover, AKPs induced the secretion and expression of bone morphogenetic protein 2 (BMP- 2) and triggered the activation of BMP2-dependent Smads signaling. AKPs also activated Wnt/ β-catenin signaling, and synergistically activated the expression of Runt-related transcription factor 2 (Runx 2) and Osterix (OSX).

Conclusion: AKPs promoted longitudinal bone growth by activating GH/IGF-1 axis, BMP-2/Smads and Wnt/β-catenin pathways, suggesting AKPs to be a potential nutrient fortifier for longitudinal bone growth.

背景：随着生活水平的提高，身高越来越受到关注。营养不良是儿童身材矮小的主要原因之一；因此，青春期的营养干预是预防身材矮小的关键。来自南极磷虾 (AKP) 的肽是理想的蛋白质模型，可用于骨形成和抗骨质疏松症。然而，关于AKPs促进纵向骨生长的研究尚未见报道。

方法：3周龄雄性ICR小鼠，构建青春期小鼠模型，随机分为3组：正常组、酪蛋白组（酪蛋白，300 mg/kg·BW）和AKPs组（AKPs，300 mg/kg） ·体重）。给药21天后，探讨AKPs对小鼠血清生化指标和股骨组织形态学的影响，探讨AKPs促进纵向骨生长的机制。

结果：AKPs 显着增加纵向骨生长并提高骨强度。此外，AKPs显着促进生长板中软骨细胞的增殖和肥大。进一步的机制表明，AKPs 增加了血清生长激素（GH）和胰岛素样生长因子-1（IGF-1）的含量，从而激活了下游的 GH/IGF-1 轴信号通路。此外，AKP 诱导骨形态发生蛋白 2 (BMP-2) 的分泌和表达，并触发 BMP2 依赖性 Smads 信号传导的激活。AKPs 还激活 Wnt/β-catenin 信号，并协同激活 Runt 相关转录因子 2 (Runx 2) 和 Osterix (OSX) 的表达。

结论：AKPs 通过激活 GH/IGF-1 轴、BMP-2/Smads 和 Wnt/β-catenin 通路促进纵向骨生长，表明 AKPs 是纵向骨生长的潜在营养强化剂。