Nf2调控beta-arrestin2偏向性PTH1R信号偶联骨量与骨骼完整性的机制研究
Nf2 orchestrates β-arrestin2-biased PTH1R signaling to couple bone mass with skeletal integrity
Junguang Liao, Yiliang He, Chenyang Zhang, Qitao Qian, Yuping Huang, Qi Zhang, Panpan Shen, Chenhe Zhou, Mengrui Wu, Guiqian Chen
Journal：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
IF：9.5
DOI：10.1073/pnas.2524671123
PMID：
Published：2026-06-10
research field：分子生物学内分泌学骨生物学骨骼发育细胞信号转导
Abstract
Significance This study identifies neurofibromin 2 (Nf2) as a critical regulator of parathyroid hormone (PTH) and PTH-related peptide (PTHrP) signaling. Nf2 specifically promotes β-arrestin2-coupled receptor internalization, decoupling this endocytic pathway from canonical G-protein signaling. This mechanism critically determines skeletal homeostasis by influencing bone anabolism and catabolism. Our findings establish Nf2 as a chondrocyte-intrinsic modulator of PTH1R trafficking, providing a mechanistic basis for understanding how bone balances its structure and integrity, where both bone mass and quality are comprised.
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