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Published on: November 16, 2011
Hyperglycemia induces endoplasmic reticulum stress-dependent CHOP expression in osteoblasts
Wei Liu1, Xiaoqing Zhu, Qian Wang
1Department of Prosthetics, Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, P.R. China.
Experimental and Therapeutic Medicine
|June 6, 2013
Summary
Hyperglycemia in diabetes causes bone loss by disrupting endoplasmic reticulum (ER) homeostasis, leading to increased C/EBP-homologous protein (CHOP) expression and osteoblast apoptosis, contributing to diabetic osteoporosis.
Area of Science:
- Endocrinology
- Metabolic Bone Diseases
- Cell Biology
Background:
- Diabetic osteoporosis is a significant global health issue.
- Hyperglycemia in diabetes mellitus leads to osteopenia and increased bone fragility.
- The precise molecular mechanisms underlying diabetic osteoporosis remain largely unknown.
Purpose of the Study:
- To investigate the role of endoplasmic reticulum (ER) homeostasis and C/EBP-homologous protein (CHOP) in diabetic osteoporosis.
- To determine if hyperglycemia-induced ER stress and CHOP activation contribute to osteoblast apoptosis.
Main Methods:
- Diabetic rat models were established using streptozotocin (STZ) injection.
- Osteoblasts were cultured in high-glucose medium in vitro.
- Bone mineral density (BMD), femur pathology, and CHOP expression in osteoblasts were assessed using immunohistochemistry and western blot.
Main Results:
- Diabetic rats exhibited significantly reduced BMD and fewer osteoblasts in the femur after six weeks.
- Exposure to high-glucose medium in vitro also reduced osteoblast numbers.
- The expression of the ER stress regulator CHOP was significantly elevated in osteoblasts from diabetic rats and those cultured in high-glucose conditions (P<0.01).
Conclusions:
- Hyperglycemia in diabetes elevates CHOP expression, contributing to osteoblast apoptosis and the development of diabetic osteoporosis.
- Elevated CHOP expression is implicated as a key factor in the pathogenesis of diabetic osteoporosis.
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