Research identifies cellular copper overload as a primary driver of bone tissue destruction in inflammatory diseases

Wuhan University researchers find that copper metabolism and glycogen synthesis are key factors in bone diseases like arthritis and osteoporosis.

By: AXL Media

Published: Mar 5, 2026, 9:51 AM EST

Source: The information in this article was sourced from West China School of Stomatology, Sichuan University

Mechanism of inflammatory osteolysis identified

Inflammatory osteolysis is a progressive condition characterized by the destruction of bone tissue, frequently observed in patients with rheumatoid arthritis, osteoporosis, and chronic apical periodontitis. This skeletal decay is driven by a combination of immune hyperactivation and an increase in osteoclasts, which are cells specialized in degrading bone. While copper is an essential element for collagen deposition in healthy bones, researchers have discovered that dysregulated levels of this metal can trigger cuproptosis, a specific form of programmed cell death that exacerbates bone weakening.

Copper overload disrupts cellular energy pathways

A research team led by Professor Lu Zhang investigated the role of copper metabolism in bone tissue affected by periodontitis in both human and animal models. Their study found that excessive intracellular copper directly interferes with the transcription of Glycogen Synthase 1, an enzyme required to convert glucose into stored glycogen. By binding to histone proteins in chromosomes, copper effectively silences the gene responsible for glycogen synthesis. This metabolic shift forces cells to break down existing glycogen into glucose for rapid energy production, a process that correlates with the severity of bone loss in the jaw.

Oxidative stress and immune cell transformation

The disruption of glycogen synthesis has significant downstream effects on the pentose phosphate pathway, which normally produces the reducing agents necessary to mitigate oxidative stress. When copper levels are too high, glucose is diverted away from this protective pathway, leading to increased oxidative damage within the cell. The researchers observed that this environment causes macrophages to transform into bone degrading osteoclasts. This transformation occurred both during natural copper overload and when chemical inhibitors were used to block glycogen synthesis, suggesting a direct link between metabolic health and bone density.