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Zinc Deficiency Alters the Distribution of Calcium in the Body and Decreases Bone Mineral Density by Inhibiting
Hua Ning1, Jiali Zhao2, Xiaocai Huang3
1National Key Disciplines of Nutrition and Food Hygiene, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China; School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Harbin, China.
Background:
Zinc (Zn) is an essential trace element for bone growth and development and for maintaining bone mineral density (BMD). Although Zn deficiency is known to disrupt calcium (Ca) metabolism, it remains unclear whether this metabolic disturbance directly underlies the associated reduction in BMD.
Objectives:
The study aimed to clarify how Zn deficiency affects BMD by disrupting systemic Ca metabolism.
Methods:
This study consisted of 2 animal experiments. In experiment 1, 35-day-old male Wistar rats were fed a normal Zn diet (30 mg/kg; NZG), a low Zn diet (10 mg/kg; LZG), or a pair-fed Zn diet (30 mg/kg; PZG) for 4 wk. In experiment 2, 28-d-old male Wistar rats received the same dietary treatments for 5 wk. Femoral weight, length, morphology; and BMD; as well as Ca and calmodulin (CaM) concentrations were measured. Complementary cellular and molecular experiments were conducted to validate the in vivo findings and explore the underlying mechanisms. Group differences were evaluated using independent t-tests and analysis of variance.
Results:
In both animal experiments, the LZG group demonstrated significantly lower femoral weight and BMD than the NZG and PZG groups (P < 0.05). In experiment 2, LZG rats additionally showed shorter femoral length, reduced trabecular number, and decreased cortical thickness. Furthermore, these rats exhibited lower Ca concentrations in urine, feces, and liver but higher concentrations in serum and skeletal muscle (P < 0.05), indicating that Zn deficiency perturbs systemic Ca distribution across tissues. Serum and skeletal muscle CaM concentrations were also reduced (P < 0.05). Corroborating these in vivo findings, low Zn culture conditions in mouse skeletal muscle cells elevated intracellular Ca concentrations and downregulated CaM expression at both mRNA and protein concentrations. Notably, overexpression of CaM1 reversed the intracellular Ca dysregulation induced by Zn deficiency.
Conclusions:
Our results indicate that CaM plays a key role in Ca dysregulation and BMD reduction caused by Zn deficiency.
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