1. Academic Validation
  2. Progranulin, a moderator of estrogen/estrogen receptor α binding, regulates bone homeostasis through PERK/p-eIF2 signaling pathway

Progranulin, a moderator of estrogen/estrogen receptor α binding, regulates bone homeostasis through PERK/p-eIF2 signaling pathway

  • J Mol Med (Berl). 2022 Aug;100(8):1191-1207. doi: 10.1007/s00109-022-02233-z.
Yuyou Yang  # 1 Naibo Feng  # 1 Li Liang 1 Rong Jiang 2 Yiming Pan 1 Nana Geng 1 Mengtian Fan 1 Xiaoli Li 1 Fengjin Guo 3
Affiliations

Affiliations

  • 1 Department of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing, 400016, China.
  • 2 Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing, 400016, China.
  • 3 Department of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing, 400016, China. [email protected].
  • # Contributed equally.
Abstract

Under normal conditions, the human body employs the synergistic action of osteoblasts and osteoclasts to maintain a dynamic balance between bone formation and resorption. Bone homeostasis plays a very important role in the process of bone formation. Various bone diseases can occur if bone homeostasis is disrupted. In this study, the serum estrogen levels were significantly increased in the granulin (GRN)-deficient mice and PGRN regulates the binding of estrogen and Estrogen Receptor α (ERα) and then affects estrogen's ability to regulate bone formation and resorption. In addition, this study also explored the role that PGRN plays in regulating bone homeostasis by affecting the binding of estrogen and estrogen receptors through the protein kinase R-like endoplasmic reticulum kinase/phosphorylation of the eukaryotic initiation factor 2 signaling pathway. In summary, we confirmed the important role of PGRN in regulating the estrogen (E2)/ERα signal in maintaining bone homeostasis. Our findings may provide a new strategy for the treatment of osteoporosis and maintaining bone homeostasis. KEY MESSAGES: PGRN is a molecular regulator of the binding of E2 and ERα signal in maintaining bone homeostasis. PGRN plays in regulating bone homeostasis through the PERK/p-eIF2α signaling pathway. The best therapeutic effect of PGRN in osteoporosis is associated with different concentration of E2.

Keywords

Bone homeostasis; Estrogen; Estrogen receptor α; Progranulin.

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