Copper regulation of immune response and potential implications for treating orthopedic disorders

Abstract

Copper is an indispensable trace metal element in human body, and copper deficiency is rare in clinic. However, diseases associated with serum copper deficiency, such as leukopenia, neutropenia, arthritis, osteoporosis, and bone defects, are well known. Copper ions can also achieve the effect of fighting pathogenic bacteria through the “contact killing” characteristic. Copper ion is also an important cofactor of bone matrix synthase, plays an important role in the pathophysiology of orthopedic diseases. The present review highlights the biological functions of copper in immunity, bone diseases and stem cells, as well as potential drug development targeting copper status for diagnostics and therapeutics of copper-associated bone diseases.

Targeting bone homeostasis regulation: potential of traditional Chinese medicine flavonoids in the treatment of osteoporosis

“…Copper death is distinct from iron death and oxidative stress in terms of the underlying mechanism that triggers OP. The phenomenon is closely related to immune factors and directly mediates the skeletal system/immune system balance ( Xu et al, 2018 ; Liu et al, 2022 ). Similarly, TCM plants have significant potential for the study of copper death on OP.…”

Copper trafficking systems in cells: insights into coordination chemistry and toxicity

“…In line with the impact of copper on cell apoptosis, the imbalance in copper levels could activate various transcription factors including MAPK, nuclear factor kappa-B (NF-κB), and p53, thereby playing a role in the pathogenesis of cancer, cardiovascular disease, or arthritis, which may extend beyond the scope of this review (see ref. 159–162).…”

Unravelling the Mystery of COVID‐19 Pathogenesis: Spike Protein and Cu Can Synergize to Trigger ROS Production

“…Although these results show the negative role of oxidative stress in COVID‐19, the mechanism of ROS generation remains unknown. Our hypothesis is that SARS‐CoV‐2 initiates inflammation, resulting in elevated concentrations of copper [35] . These metal ions can coordinate to the S protein and induce production of hydroxyl radicals, which damage all biomolecules.…”

“…Our hypothesis is that SARS-CoV-2 initiates inflammation, resulting in elevated concentrations of copper. [35] These metal ions can coordinate to the S protein and induce production of hydroxyl radicals, which damage all biomolecules. To confirm this hypothesis, we used the 1151-1159 fragment of the spike protein from the SARS-CoV-2 Wuhan variant (Ac-ELDKYFKNH-NH 2 , L1) and the 1267-1274 fragment from its beta variant (Ac-WSHPQFEK-NH 2 , L2; Figure S1).…”