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The endoplasmic reticulum proteostasis network and bone disease
Hesso Farhan1, Muhammad Zahoor2, Josephine T Tauer3
1Institute of Pathophysiology, Medical University of Innsbruck, Innsbruck, Austria.
Trends in Molecular Medicine
|July 11, 2025
Summary
Endoplasmic reticulum (ER) proteostasis is crucial for bone health. Defects in ER protein quality control are linked to skeletal disorders, suggesting new therapeutic targets for bone diseases.
Area of Science:
- Bone biology
- Cellular biology
- Molecular medicine
Background:
- Bone homeostasis depends on osteoblasts, osteoclasts, and osteocytes.
- Proteostasis, managed by the endoplasmic reticulum (ER), is vital for bone cell function, including collagen type I secretion.
- ER proteostasis defects are increasingly implicated in skeletal disorders affecting bone development and mass.
Purpose of the Study:
- To explore the mechanisms of ER proteostasis and the unfolded protein response (UPR).
- To discuss how genetic, metabolic, and environmental factors disrupt ER proteostasis in bone.
- To highlight potential therapeutic strategies targeting ER-Golgi traffic and ER stress for bone diseases.
Main Methods:
- Review of current literature on ER proteostasis and bone biology.
- Analysis of the role of the unfolded protein response (UPR) in skeletal health.
- Discussion of factors contributing to ER stress in bone cells.
Main Results:
- ER proteostasis is essential for normal bone cell function and skeletal integrity.
- Disruptions in ER protein quality control pathways contribute to impaired bone development and reduced bone mass.
- Genetic, metabolic, and environmental factors can exacerbate ER stress, leading to bone pathology.
Conclusions:
- ER proteostasis is a critical determinant of skeletal health.
- Understanding ER stress mechanisms in bone offers potential for novel therapeutic interventions.
- Targeting ER-Golgi transport and ER stress may provide new avenues for treating bone diseases.
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