Astragalus Extract Mixture HT042 Increases Longitudinal Bone Growth Rate by Upregulating Circulatory IGF-1 in Rats.

Donghun Lee,Jungbin Song,Hocheol Kim,Sung Hyun Lee,Yoon Hee Lee

doi:10.1155/2017/6935802

Abstract

Astragalus extract mixture HT042 is a standardized ingredient of health functional food approved by Korean FDA with a claim of “height growth of children.” HT042 stimulates bone growth rate and increases local IGF-1 expression in growth plate of rats which can be considered as direct stimulation of GH and its paracrine/autocrine actions. However, it remains unclear whether HT042 stimulates circulatory IGF-1 which also plays a major role to stimulate bone growth. To determine the effects on circulatory IGF-1, IGF-1 and IGFBP-3 expressions and phosphorylation of JAK2/STAT5 were evaluated in the liver after 10 days of HT042 administration. HT042 upregulated liver IGF-1 and IGFBP-3 mRNA expression, IGF-1 protein expression, and phosphorylation of JAK2/STAT5. HT042 also increased bone growth rate and proliferative zonal height in growth plate. In conclusion, HT042 stimulates bone growth rate via increment of proliferative rate by upregulation of liver IGF-1 and IGFBP-3 mRNA followed by IGF-1 protein expression through phosphorylation of JAK2/STAT5, which can be regarded as normal functioning of GH-dependent endocrine pathway.

Highlights

Longitudinal bone growth is the result of chondrocyte proliferation and ensuing hypertrophy in growth plates, called endochondral ossification which is mainly controlled by a system of growth hormone- (GH-) insulin-like growth factor-1 (IGF-1) axis [1]
Circulatory IGF-1 is biosynthesized in the liver as an endocrine hormone in the ternary form bound to IGF binding protein-3 (IGFBP-3) and acid labile subunit (ALS), while IGF-1 is expressed by nonliver tissues including growth plate, where it works in a paracrine/autocrine fashion
Years later, the same team revealed that circulatory IGF-1 is important for maintaining normal growth by the study that liver IGF-1 and ALS double knockout mice were much smaller because there was a decrease in IGF-1 production and circulatory IGF-1 stability that originated from compensatory nonliver sources because of the absence of protective ALS protein [3]

Summary

Introduction

Longitudinal bone growth is the result of chondrocyte proliferation and ensuing hypertrophy in growth plates, called endochondral ossification which is mainly controlled by a system of growth hormone- (GH-) insulin-like growth factor-1 (IGF-1) axis [1]. Years later, the same team revealed that circulatory IGF-1 is important for maintaining normal growth by the study that liver IGF-1 and ALS double knockout mice were much smaller because there was a decrease in IGF-1 production and circulatory IGF-1 stability that originated from compensatory nonliver sources because of the absence of protective ALS protein [3]. This suggests that circulatory IGF-1 plays a major role in longitudinal bone growth rate

Methods

Results

Conclusion