Thioredoxin Interacting Protein Expressed in Osteoblasts Mediates the Anti-Proliferative Effects of High Glucose and Modulates the Expression of Osteocalcin.

Abstract

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. 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). 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. Our findings indicate that Txnip is an intracellular mediator of the anti-proliferative effects of extracellular high glucose levels on osteoblasts.