Dietary zinc supplementation increased TNFα and IL1β-induced RANKL expression, resulting in a decrease in bone mineral density in rats

Abstract

We investigated the effect of dietary zinc supplementation on bone metabolism in rats. Four-week-old male Wistar rats were fed a 30.0 mg zinc/kg diet (C), a 300.0 mg zinc/kg diet (HZ) or a 3,000.0 mg zinc/kg diet (EZ) for 4 weeks. The zinc content of the femur gradually increased in accordance with the gradual increase in the dietary zinc level. Although the mRNA expression of zinc transporters in bone did not differ between the groups, the mRNA expression of metallothioneins was increased in the HZ and EZ groups compared to the C group. Moreover, the bone mineral density was significantly decreased in the HZ and EZ groups compared to the C group. Furthermore, the mRNA expression of tumor necrosis factor α, Interleukin-1β and osteoclastogenesis-related genes such as receptor for activator of nuclear factor-κB (NF-κB) ligand, tumor necrosis factor receptor-associated factor 6, and nuclear factor of activated T cells cytoplasmic 1 was significantly increased in the HZ and EZ groups compared to the C group. These findings suggested that dietary zinc supplementation reduced bone mineral density through the promotion of bone resorption via an increase in the expression of receptor for activator of NF-κB ligand induced by tumor necrosis factor α and Interleukin-1β.

A short-term zinc-deficient diet decreases bone formation through down-regulated BMP2 in rat bone

“…4) The serum levels of osteocalcin and the C-terminal telopeptide of type I collagen (CTx) were measured as described previously. 8) Extraction of total RNA and synthesis of complementary DNA were performed as described previously. 8) For real-time PCR, the reaction mixture was prepared using the TaqMan Gene Expression Master Mix (Applied Biosystems, Foster, CA) with TaqMan gene expression assays (Applied Biosystems) for the following rat genes: Zip1, Zip13, Zip14, ZnT5, ZnT7, metallothionein (Mt)1a, Mt2A, bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), Osterix, alkaline phosphatase (ALP), Osteocalcin, Collagen typeⅠα 1(Col1a1), and β-actin.…”

“…Respective Assay IDs were described previously. 8,9) Gene transcript levels in each sample were determined using the relative standard curve method. The level of gene transcripts is expressed as a ratio relative to βactin mRNA, with the level in rats fed the control diet set to 1.…”

Can Zinc Correction in SARS-CoV-2 Patients Improve Treatment Outcomes?

“…Importantly, Zinc deficiency is associated with the excessive and tissue-damaging proinflammatory release of cytokines, including increased tumor necrosis factor-alpha (TNF-α) 33,34 and IL-6 35 .…”

“…Notably, Zinc correction is associated with the down-regulation of tumor necrosis factor-alpha 30,33,34 .…”

β-Carotene prevents bone loss in hind limb unloading mice

“…( 12 ) On the other hand, it is known that high phosphorus intake acutely and adversely affects bone metabolism in healthy young females. ( 15 ) Suzuki et al ( 16 ) reported that excessive intake of zinc leads to bone resorption and bone loss in rats.…”