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Published on: March 1, 2022
Thioredoxin Interacting Protein Expressed in Osteoblasts Mediates the Anti-Proliferative Effects of High Glucose and
Sarah McGarry1,2, Karen Kover1,2, Francesco De Luca1,2
1Division of Endocrinology, Children's Mercy Hospitals, Kansas City, MO, USA.
Background:
Hyperglycemia is associated with impaired bone health in patients with diabetes mellitus. Although a direct detrimental effect of hyperglycemia on the bone has been previously reported, the specific molecular mediator(s) responsible for the inhibitory effect of high glucose levels on the bone remains unclear. We hypothesized that thioredoxin-interacting protein (Txnip), an essential mediator of oxidative stress, is such a mediator.
Methods:
We cultured MG-63 cells (immortalized human osteoblasts) with normal or high glucose concentrations and transfected them with scrambled or Txnip-specific small interfering RNA (siRNA).
Results:
High glucose levels increased Txnip expression and reduced MG-63 cell proliferation. The high-glucose level mediated reduction in cell proliferation was prevented in Txnip siRNA-transfected cells. In addition, we demonstrated that silencing Txnip mRNA expression in osteoblasts reduced the expression of the osteocalcin gene. Our results suggest that high glucose levels or silencing of Txnip mRNA expression may induce apoptosis in osteoblasts.
Conclusions:
Our findings indicate that Txnip is an intracellular mediator of the anti-proliferative effects of extracellular high glucose levels on osteoblasts.
Insights
High glucose impairs bone health by increasing thioredoxin-interacting protein (Txnip) in osteoblasts. Reducing Txnip prevents this effect, suggesting Txnip is key to hyperglycemia’s detrimental impact on bone cells.
Area of Science:
- Biochemistry
- Molecular Biology
- Bone Biology
Background:
- Hyperglycemia in diabetes mellitus is linked to poor bone health.
- The molecular mechanisms by which high glucose affects bone cells are not fully understood.
- Thioredoxin-interacting protein (Txnip) is a potential mediator of oxidative stress and cellular dysfunction.
Purpose of the Study:
- To investigate the role of thioredoxin-interacting protein (Txnip) as a molecular mediator of high glucose-induced effects on osteoblasts.
- To determine if Txnip mediates the inhibitory effects of hyperglycemia on bone cell proliferation and survival.
Main Methods:
- Cultured human osteoblast-like MG-63 cells under normal and high glucose conditions.
- Utilized small interfering RNA (siRNA) to silence Txnip expression in osteoblasts.
- Assessed cell proliferation, Txnip expression, and osteocalcin gene expression.
Main Results:
- High glucose significantly increased Txnip expression in MG-63 cells.
- High glucose reduced osteoblast proliferation, an effect reversed by Txnip silencing.
- Silencing Txnip also reduced osteocalcin gene expression, suggesting a role in bone matrix formation.
- Both high glucose and Txnip silencing showed potential to induce osteoblast apoptosis.
Conclusions:
- Txnip acts as an intracellular mediator for the anti-proliferative effects of high glucose on osteoblasts.
- Targeting Txnip may offer a therapeutic strategy to mitigate hyperglycemia-induced bone damage in diabetes.
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