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<p>The molecular mechanisms underlying growth hormone (GH) therapy in children with idiopathic short stature (ISS) remain incompletely understood. This study investigated how GH promotes bone growth in children with ISS, focusing on insulin-like growth factor-binding protein 2 (IGFBP2) and thrombospondin-1 (THBS1). Analysis of ISS patient plasma showed downregulated IGFBP2, predicted to interact strongly with THBS1. Experiments using human chondrocytes revealed that GH treatment stimulated cell proliferation, accelerated the cell cycle, and induced hypertrophic differentiation, marked by increased expression of proteins like COL10A1, RUNX2, OCN, OPN, and alkaline phosphatase activity. GH also elevated IGFBP2 and insulin-like growth factor-1 (IGF-1) while suppressing THBS1. Crucially, knocking down IGFBP2 blocked these GH effects, reducing proliferation, halting cell cycle progression, decreasing differentiation markers and IGF-1, while increasing THBS1. Conversely, overexpressing IGFBP2 mimicked GH's effects. Importantly, silencing IGFBP2 partially prevented GH-induced proliferation, differentiation, and IGF-1 secretion. This demonstrates that IGFBP2 acts as a key mediator of GH's action by inhibiting THBS1, which subsequently activates the IGF-1 pathway to drive chondrocyte proliferation and hypertrophic differentiation. The IGFBP2-THBS1 axis is thus a core mechanism for GH therapy in ISS, offering a novel therapeutic target for improving treatment.&#xa0;</p>

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Growth hormone therapy promotes bone growth in idiopathic short stature children by activating the IGF-1 pathway via IGFBP2-mediated inhibition of THBS1

  • 期刊论文

  • 发表日期：

    2025年11月5日

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  • Haiyan Liu,
  • Qin Zhao

摘要

The molecular mechanisms underlying growth hormone (GH) therapy in children with idiopathic short stature (ISS) remain incompletely understood. This study investigated how GH promotes bone growth in children with ISS, focusing on insulin-like growth factor-binding protein 2 (IGFBP2) and thrombospondin-1 (THBS1). Analysis of ISS patient plasma showed downregulated IGFBP2, predicted to interact strongly with THBS1. Experiments using human chondrocytes revealed that GH treatment stimulated cell proliferation, accelerated the cell cycle, and induced hypertrophic differentiation, marked by increased expression of proteins like COL10A1, RUNX2, OCN, OPN, and alkaline phosphatase activity. GH also elevated IGFBP2 and insulin-like growth factor-1 (IGF-1) while suppressing THBS1. Crucially, knocking down IGFBP2 blocked these GH effects, reducing proliferation, halting cell cycle progression, decreasing differentiation markers and IGF-1, while increasing THBS1. Conversely, overexpressing IGFBP2 mimicked GH's effects. Importantly, silencing IGFBP2 partially prevented GH-induced proliferation, differentiation, and IGF-1 secretion. This demonstrates that IGFBP2 acts as a key mediator of GH's action by inhibiting THBS1, which subsequently activates the IGF-1 pathway to drive chondrocyte proliferation and hypertrophic differentiation. The IGFBP2-THBS1 axis is thus a core mechanism for GH therapy in ISS, offering a novel therapeutic target for improving treatment.