By regulating the IP3R/GRP75/VDAC1 complex to restore mitochondrial dynamic balance, selenomethionine reduces lipopolysaccharide-induced neuronal apoptosis.

Selenium (Se), as one of the essential trace elements, plays an anti-inflammatory, antioxidation, and immune-enhancing effect in the body. In addition, Se can also improve nervous system damage induced by various factors. Earlier studies have described the important role of mitochondrial dynamic imbalance in lipopolysaccharide (LPS)-induced nerve injury. The inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (GRP75)/voltage-dependent anion channel 1 (VDAC1) complex is considered to be the key to regulating mitochondrial dynamics. However, it is not clear whether Selenomethionine (SeMet) has any influence on the IP3R/GRP75/VDAC1 complex. Therefore, the aim of this investigation was to determine whether SeMet can alleviate LPS-induced brain damage and to elucidate the function of the IP3R/GRP75/VDAC1 complex in it. We established SeMet and/or LPS exposure models in vivo and in vitro using laying hens and primary chicken nerve cells. We noticed that SeMet reversed endoplasmic reticulum stress (ERS) and the imbalance in mitochondrial dynamics and significantly prevented the occurrence of neuronal apoptosis. We made this finding by morphological observation of the brain tissue of laying hens and the detection of related genes such as ERS, the IP3R/GRP75/VDAC1 complex, calcium signal (Ca2+), mitochondrial dynamics, and apoptosis. Other than that, we also discovered that the IP3R/GRP75/VDAC1 complex was crucial in controlling Ca2+ transport between the endoplasmic reticulum and the mitochondrion when SeMet functions as a neuroprotective agent. In summary, our results revealed the specific mechanism by which SeMet alleviated LPS-induced neuronal apoptosis for the first time. As a consequence, SeMet has great potential in the treatment and prevention of neurological illnesses (like neurodegenerative diseases).

Insight into the mechanism of melatonin in attenuating PCB126-induced liver injury: Resistance to ROS-dependent NETs formation to alleviate inflammation and lipid metabolism dysfunction.

3,3',4',4',5-Polychlorinated biphenyls (PCB126) is classified as a persistent organic environmental pollutant that can cause liver damage by producing excessive reactive oxygen species (ROS). ROS also can stimulate neutrophil extracellular traps (NETs) formation, which cause damage to organism if NETs are produced in excess. Melatonin is generally considered to possess strong antioxidant and anti-inflammation prosperities, but it is unclear whether it can alleviate PCB126-induced injury. To explore whether PCB126-induced liver injury is related to the formation of NETs and whether melatonin has a potent protective effect, we established PCB126 exposure/ PCB126 and melatonin co-treatment mouse models by gavage. To further clarify the specific mechanism, we also cultured neutrophils and AML12 cells to replicate in vivo model. Here, we found PCB126 exposure resulted in an elevation in the activities of MDA, LPO, PCO, and 8-OHdG, and a reduction in the activities of CAT, GSH-PX and SOD. We found that PCB126 exposure led to an elevation in the expression levels of chemokines (CCL2, CCL3, CCL4, CXCL12, and CXCL8) and marker factors for NETs formation (MPO, NE, NOX2, PKCα, and PKCζ) in the PCB126 group. IF, SYTOX staining, and SEM results also revealed that PCB126 could stimulate NETs formation. In addition, results of a co-culture system of PBNs and AML12 cells revealed that the expression levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α) significantly decreased and the expression levels of metabolism factors (Fas, Acc, and Srebp) slightly decreased for scavenging NETs, indicating NETs formation aggravated PCB126-induced hepatic damages. Noteworthy, treatment with melatonin reversed these results. In summary, our findings revealed that melatonin alleviated hepatic damage aggravated by PCB126-induced ROS-dependent NETs formation through suppressing excessive ROS production. This finding not only enriches toxicological mechanism of PCB126, but more importantly extends biological effects of melatonin and its potential application values.

In vitro and in silico analyses reveal the toxicity of metolachlor to grass carp hepatocytes and the antagonism of melatonin.

Due to the widespread use of metolachlor (MET), the accumulation of MET and its metabolites in the environment has brought serious health problems to aquatic organisms. At present, the toxicity of MET on the physiological metabolism of aquatic animals mainly focused on the role of enzymes. There is still a lack of research on the molecular mechanisms of MET hepatotoxicity, especially on antagonizing MET toxicity. Therefore, this study focuses on grass carp hepatocytes (L8824 cells) closely related to toxin accumulation. By establishing a MET exposed L8824 cells model, it is determined that MET exposure induces pyrolytic inflammation of L8824 cells. Subsequent mechanistic studies found that MET exposure induces pyroptosis in L8824 cells through mitochondrial dysfunction, and siCaspase-1 inhibits the MET induced ROS production, suggesting a regulation of ROS-NLRP3- Caspase-1 pyroptotic inflammation cycling center in MET induced injury to L8824 cells. Molecular docking revealed a strong binding energy between melatonin (MT) and Caspase-1. Finally, a model of L8824 cells with MT intervention in MET exposure was established. MT can antagonize the pyroptosis induced by MET exposure in L8824 cells by targeting Caspase-1, thereby restoring mitochondrial function and inhibiting the ROS-pyroptosis cycle. This study discovered targets and mechanisms of MT regulating pyroptosis in MET exposed-L8824 cells, and the results are helpful to provide new targets for the design of MET antidotes.

Cannabidiol alleviates perfluorooctane sulfonate-induced macrophage extracellular trap mediate inflammation and fibrosis in mice liver.

As a new type of persistent organic pollutant, perfluorooctane sulphonate (PFOS) has received extensive attention worldwide. Cannabidiol (CBD) is a non-psychoactive natural cannabinoid extract that has been proved to have antioxidation, regulation of inflammation and other functions. However, the effects of PFOS on liver injury and whether CBD can alleviate PFOS-induced liver injury are still unclear. Therefore, in this study, we used CBD (10 mg/kg) and/or PFOS (5 mg/kg) to intraperitoneally inject mice for 30 days. We found that PFOS exposure led to inflammatory infiltration in the liver of mice, increased the formation of macrophage extracellular trap (MET), and promoted fibrosis. In vitro, we established a coculture system of RAW264.7, AML12 and LX-2 cells, and treated them with CBD (10 µM) and/or PFOS (200 µM). The results showed that PFOS could also induce the expression of MET, inflammation and fibrosis marker genes in vitro. Coiled-coil domain containing protein 25 (CCD25), as a MET-DNA sensor, was used to investigate its ability to regulate inflammation and fibrosis, we knocked down CCDC25 and its downstream proteins (integrin-linked kinase, ILK) by siRNA technology, and used QNZ to inhibit NF-κB pathway. The results showed that the knockdown of CCDC25 and ILK and the inhibition of NF-κB pathway could inhibit MET-induced inflammation and fibrosis marker gene expression. In summary, we found that PFOS-induced MET can promote inflammation and fibrosis through the CCDC25-ILK-NF-κB signaling axis, while the treatment of CBD showed a protective effect, and it is proved by Macromolecular docking that this protective effect is achieved by combining CBD with peptidylarginine deiminase 4 (PAD4) to alleviate the release of MET. Therefore, regulating the formation of MET and the CCDC25-ILK-NF-κB signaling axis is an innovative treatment option that can effectively reduce hepatotoxicity. Our study reveals the mechanism of PFOS-induced hepatotoxicity and provides promising insights into the protective role of CBD in this process.

Perfluorooctane sulfonate-induced apoptosis in kidney cells by triggering the NOX4/ROS/JNK axis and antagonism of cannabidiol.

Perfluorooctane sulfonate (PFOS) is one of the persistent organic pollutants (POPs), which can cause severe nephrotoxicity in mammals. Cannabinol (CBD), a nonpsychoactive cannabinoid obtained from the cannabis plant, has attracted attention in recent years for its excellent antioxidant properties. NADPH oxidase 4 (NOX4) has an important effect in supporting normal renal physiological function. The potential mechanisms of PFOS nephrotoxicity and whether CBD can prevent renal damage caused by PFOS remain unclear. This work aimed to study the mechanisms of PFOS-induced kidney damage and the protective role of CBD against PFOS-induced kidney damage. We demonstrated that PFOS led to renal insufficiency and structural damage in mice, induced overexpression of NOX4 and the onset of oxidative stress, and activated apoptosis of the mitochondrial pathway via the JNK signaling pathway. However, treatment with CBD reversed these changes. For further investigation of the potential mechanism of PFOS-induced renal cell apoptosis, the expression of NOX4 was inhibited in vitro experiments using Apocynin, an effective NOX4 inhibitor. The outcomes showed that PFOS-induced ROS production and JNK signaling pathway activation and apoptosis in human embryonic kidney (HEK293) cells were significantly reduced after inhibition of NOX4. This suggests that PFOS-induced NOX4 overexpression serves as an upstream event for JNK pathway activation. In conclusion, the findings suggest that PFOS induces apoptosis in renal cells via the NOX4/ROS/JNK pathway. Meanwhile, CBD alleviated PFOS-induced renal apoptosis through the inhibition of NOX4/ROS/JNK axis activation.

Melatonin alleviates 3,3',4,4',5-pentachlorobenzene induced colon injury by relieving oxidative stress.

3,3',4,4',5-pentachlorobiphenyl (PCB126) is widely distributed, non-degradable and bioaccumulative, which can affect the function of tissues and organs of the living organisms. Melatonin (MT) is a sort of indole neurohormone that is mainly secreted by the pineal gland. Numerous studies have shown that MT can alleviate intestinal injury through various mechanisms such as antioxidant, anti-inflammatory, and anti-apoptosis. For the above reasons, the aim of this study is to explore the mechanism of intestinal injury in mice after exposure to PCB126 as well as the antagonistic effect of MT. Mice were respectively fed PCB126 (0.326 mg/kg) and/or MT (10 mg/kg) in vivo. In vitro, colonic epithelial cells (MCEC) were treated with PCB126 (150 µM) and/or MT (2 mM). We found that the microscopic structure of colon tissue was impaired after exposure to PCB126. The levels of oxidative stress, the protein and mRNA levels of expression of inflammatory related factors were significantly increased and the expression levels of intestinal tight junction protein were decreased. Notably, MT can promote Nrf2/HO-1 expression level and reduce the colonic injury caused by PCB126. Further in vitro treatment with reactive oxygen species inhibitors (NAC) showed that it significantly alleviated PCB126-induced in MCEC cell damage. In summary, the above results suggested that MT alleviates PCB126-induced colon inflammation by inhibiting the overproduction of reactive oxygen species (ROS) and up-regulating the expression level of intestinal tight junction protein. Our results contribute to the further comprehension of the intestinal toxicity effects of PCB126 and the significant role of MT in preserving the mechanisms of intestinal injury.

Selenium deficiency exacerbated Bisphenol A-induced intestinal toxicity in chickens: Apoptosis and cell cycle arrest mediated by ROS/P53.

Bisphenol A (BPA) is a phenolic organic synthetic compound that is used as the raw material of polycarbonate plastics, and its safety issues have recently attracted wide attention. Selenium (Se) deficiency has gradually developed into a global disease affecting intestinal function via oxidative stress and apoptosis. However, the toxic effects and potential mechanisms of BPA exposure and Se deficiency in the chicken intestines have not been studied. In this study, BPA exposure and/or Se deficiency models were established in vivo and in vitro to investigate the effects of Se deficiency and BPA on chicken jejunum. The results showed that BPA exposure and/or Se deficiency increased jejunum oxidative stress and DNA damage, activated P53 pathway, led to mitochondrial dysfunction, and induced apoptosis and cell cycle arrest. Using protein-protein molecular docking, we found a strong binding ability between P53 and peroxisome proliferator-activated receptor γ coactivator-1, thereby regulating mitochondrial dysfunctional apoptosis. In addition, we used N-acetyl-L-cysteine and pifithrin-α for in vitro intervention and found that N-acetyl-L-cysteine and pifithrin-α intervention reversed the aforementioned adverse effects. This study clarified the potential mechanism by which Se deficiency exacerbates BPA induced intestinal injury in chickens through reactive oxygen species/P53, which provides a new idea for the study of environmental combined toxicity of Se deficiency, and insights into animal intestinal health from a new perspective.

The mechanism of cadmium exposure-induced lymph node necroptosis and inflammation in piglets: Activation of CYP450 through VDR / CREB1 pathway.

Cadmium (Cd) is toxic non-essential heavy metal that precipitates adverse health effects in humans and animals, but the effect of Cd on lymph node toxicity of piglets is still unclear. In order to explore the possible molecular mechanism of Cd toxicity to lymph nodes of piglets, ten 6-week-old male weaned piglets were randomly divided into two groups, C group and Cd group. Group C was fed with basal diet, while group Cd was fed with basal diet supplemented with CdCl2 (20 mg/kg) for 40 days, the pigs were euthanized and the mesenteric, inguinal and submandibular lymph nodes (MLN, ILN, SLN) were collected. The results indicated that Cd could induce the inflammatory cell infiltration, microvascular hemorrhage, microthrombosis and cell necrosis in MLN, ILN and SLN of piglets, induced Cytochrome P450 proteins (CYP1A1、CYP2E1、CYP2A1 and CYP3A2) mRNA levels and the protein levels of Vitamin D receptor (VDR) and cAMP response element binding protein 1 (CREB1). In addition, Cd exposure upregulated the mRNA and protein levels of dynamin-related protein 1 (DRP1), receptor-interacting protein kinase 3 (RIP3), mixed lineage kinase domain-like protein (MLKL), and increased tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), interleukin-2 (IL-2), interleukin-4 (IL-4), cyclooxygenase 2 (COX-2) protein levels, and the damage degree of three kinds of lymph nodes was similar after Cd exposure. In general, these results manifest that Cd exposure regulates VDR/CREB1 pathway, activates CYP450s, induces necroptosis of lymph nodes, and leads to inflammation.

The mechanism of acrolein exposure inhibited the release of neutrophil extracellular traps: By reducing respiratory burst and Raf/MEK/ERK pathway and promote cell apoptosis.

Acrolein (AC) is a highly toxic volatile substance in the environment, and studies have found that excessive AC had a toxic effect on the immune system. Neutrophils are the first line of defense against pathogen invasion. The release of neutrophil extracellular traps (NETs) is a protective mechanism for neutrophils, and its release is affected by environmental pollutants. However, the effect of AC on NETs release and its mechanism remains unclear. In this study, chicken peripheral blood neutrophils were pretreated with 20 µM AC and treated with 5 µM Phorbol 12-myristate 13-acetate (PMA) to stimulate the release of NETs. The results showed that AC exposure significantly inhibited the release of NETs induced by PMA, respiratory burst, and the expression levels of phospho-rapidly accelerated fibrosarcoma (p-Raf), phospho-mitogen-activated extracellular signal-regulated kinase (p-MEK) and phospho-extracellular regulated protein kinases (p-ERK). In addition, AC exposure significantly inhibited the expression of B-cell lymphoma-2 (Bcl-2) and promoted the expression of apoptotic factors Bcl2-Associated X (Bax), cytochrome c (Cyt C), cysteinyl aspartate specific proteinase 9 (Casp 9) and cysteinyl aspartate specific proteinase 3 (Casp 3). Further inhibition of neutrophil apoptosis significantly improved the release of NETs. The above results indicated that AC exposure led to a decrease in the formation of NETs, which is caused by excessive AC-induced neutrophil apoptosis. Our study clarified the immune toxicity mechanism of AC on chickens, which is of great significance and reference value for protecting the ecological environment and poultry health.

Quercetin alleviates zearalenone-induced apoptosis and necroptosis of porcine renal epithelial cells by inhibiting CaSR/CaMKII signaling pathway.

Zearalenone (ZEA) is a mycotoxin that is highly contaminated in feed and can cause severe toxic effects on the kidneys and other organs of animals. Quercetin (QUE) is a plant-derived flavonoid with a variety of detoxification properties, but the mechanism by which QUE detoxifies the toxic effects induced by ZEA has not yet been fully elucidated. We treated porcine kidney cells (PK15) with 80 µM ZEA and/or 30 µM QUE. The results showed that ROS and MDA levels were increased, antioxidant system levels were down-regulated, anti-apoptotic factor expression levels were decreased, and apoptotic and necroptosis-related factors were up-regulated after ZAE exposure. In addition, the results of Ca2+ staining, mitochondrial membrane potential, and mitochondrial dynamics-related indicators showed that ZEA induced Ca2+ overload in PK15 cells and increased mitochondrial Ca2+ uptake (MCU expression increased). The accumulated ROS and free Ca2+ further aggravate mitochondrial damage and eventually lead to mitochondrial pathway apoptosis and necroptosis. Nevertheless, QUE targets CaSR to inhibit the CaSR/CaMKII pathway and regulate calcium homeostasis, thereby alleviating apoptosis and necroptosis mediated by mitochondrial dynamic disorder and dysfunction. The present study demonstrated the mechanism by which ZEA induces apoptosis and necroptosis in PK15 and the protective role of QUE in this process.

Cannabidiol Alleviates Perfluorooctanesulfonic Acid-Induced Cardiomyocyte Apoptosis by Maintaining Mitochondrial Dynamic Balance and Energy Metabolic Homeostasis.

Perfluorooctanesulfonic acid (PFOS), a fluorine-containing organic compound, can be widely detected in the environment and living organisms. Accumulating evidence has shown that PFOS breaks through different biological barriers resulting in cardiac toxicity, but the underlying molecular mechanisms remain unclear. Cannabidiol (CBD) is a nonpsychoactive cannabinoid without potential adverse cardiotoxicity and has antioxidant and anti-inflammatory properties that reduce multiorgan damage and dysfunction. For these reasons, the aim of this study was to research how PFOS caused heart injury and whether CBD could attenuate PFOS-induced heart injury. Mice were fed PFOS (5 mg/kg) and/or CBD (10 mg/kg) in vivo. In vitro, H9C2 cells were intervened with PFOS (200 µM) and/or CBD (10 µM). After PFOS exposure, oxidative stress levels and the mRNA and protein expression of apoptosis-related markers increased distinctly, accompanied by mitochondrial dynamic imbalance and energy metabolism disorders in mouse heart and H9C2 cells. Moreover, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, acridine orange/ethidium bromide staining and Hoechst 33258 staining signaled that the number of apoptotic cells increased after exposure to PFOS. Noteworthy, CBD simultaneous treatment alleviated a series of damages caused by PFOS-mediated oxidative stress. Our results demonstrated that CBD could alleviate PFOS-induced mitochondrial dynamics imbalance and energy metabolism disorder causing cardiomyocyte apoptosis by improving the antioxidant capacity, suggesting that CBD may represent a novel cardioprotective strategy against PFOS-induced cardiotoxicity. Our findings facilitate the understanding of the cardiotoxic effects of PFOS and the important role of CBD in protecting cardiac health.

Unraveling the mechanism of quercetin alleviating perfluorooctane sulfonate-induced apoptosis in grass carp (Ctenopharyngodon idellus) hepatocytes: AMPK/mTOR-mediated mitophagy.

Exposure to persistent new organic pollutants in the environment often leads to high mortality and causes serious economic losses to the aquaculture industry. Currently, perfluorooctane sulfonate (PFOS) is persistent and bio-accumulative in the environment, causing potential risks to aquatic ecosystems, but its toxicity mechanism to aquatic organisms is still unclear. As a natural flavonoid compound, quercetin (QU) has many biological activities such as anti-oxidation, anti-inflammatory, anti-apoptosis and immune regulation. Whether it can be used as a candidate medicine to alleviate PFOS toxicity needs to be further explored. Therefore, in this study, we treated (Ctenopharyngodon idellus) grass carp hepatocytes (L8824) with PFOS (200 µM) and/or QU (60 µM) for 24 h. The results showed that PFOS significantly increased the release of LDH and active oxygen (ROS) in L8824 cells, and led to the decrease of mitochondrial membrane potential (ΔΨm) and ATP content, the increase of mitochondrial ROS, the disorder of mitochondrial dynamics, and the initiation of Bcl-2/Bax-mediated apoptosis. Surprisingly, QU can alleviate the above PFOS-induced grass carp hepatocyte toxicity. In addition, in order to further explore the protective mechanism of QU, we used the molecular docking to predict the binding site between QU and AMPK, and found that there was a high binding capacity between QU and AMPK. In addition, we used Compound C (CC) and 3-Methyladenine (3-MA) to intervene. The results showed that CC and 3-MA intervention aggravated mitochondrial dysfunction and apoptosis factor expression in the QU+PFOS group. These data indicate that PFOS induces oxidative stress, mitochondrial dysfunction, and apoptosis. The regulation of AMPK/mTOR mediated mitophagy by QU may be a new therapeutic strategy to alleviate the hepatotoxicity of PFOS grass carp. This study provides theoretical basis and reference for exploring the toxic mechanism and biological toxic effects of PFOS, and provides a scheme for improving the economic benefits of aquaculture.

Polystyrene nanoplastics deteriorate LPS-modulated duodenal permeability and inflammation in mice via ROS drived-NF-κB/NLRP3 pathway.

The widespread occurrence of nanoplastics (NPs), has markedly affected the ecosystem and has become a global threat to animals and human health. There is growing evidence showing that polystyrene nanoparticles (PSNPs) exposure induced enteritis and the intestinal barrier disorder. Lipopolysaccharide (LPS) can trigger the inflammation burden of various tissues. Whether PSNPs deteriorate LPS-induced intestinal damage via ROS drived-NF-κB/NLRP3 pathway is remains unknown. In this study, PSNPs exposure/PSNPs and LPS co-exposure mice model were duplicated by intraperitoneal injection. The results showed that exposure to PSNPs/LPS caused duodenal inflammation and increased permeability. We evaluated the change of duodenum structure, oxidative stress parameters, inflammatory factors, and tight junction protein in the duodenum. We found that PSNPs/LPS could aggravate the production of ROS and oxidative stress in cells, activate NF-κB/NLRP3 pathway, decrease the expression tight junction proteins (ZO-1, Claudin 1, and Occludin) levels, promote inflammatory factors (TNF-α, IL-6, and IFN-γ) expressions. Duodenal oxidative stress and inflammation in PS + LPS group were more serious than those in single exposure group, which could be alleviated by NF-kB inhibitor QNZ. Collectively, the results verified that PSNPs deteriorated LPS-induced inflammation and increasing permeability in mice duodenum via ROS drived-NF-κB/NLRP3 pathway. The current study indicated the relationship and molecular mechanism between PSNPs and intestinal injury, providing novel insights into the adverse effects of PSNPs exposure on mammals and humans.

Study on the morphological and metabolic changes of femur in laying hens with hypophosphatemia.

Layer fatigue syndrome caused by the lack of calcium and phosphorus can cause fracture in laying hens. The effect of phosphorus deficiency on the femur of laying hens with layer fatigue syndrome has not been studied. In this study, sixty 22-week-old Roman white layers were randomly divided into control group (group C) and low phosphorus group (group P), 30 individuals in each group. The available phosphorus content of group P was 0.18%. At the age of 26, 30 and 34 weeks, the production performance, biomechanical index, protein expression, histopathological change of femur and serological index were detected. The results showed that the laying rate, egg quality and body weight of laying hens, bone density, cortical bone thickness, rigidity, flexural modulus, flexural rigidity, the maximum load of femur and expression of osteocalcin (OCN), receptor activator of nuclear factor kappa-Β (RANK) and receptor activator of nuclear factor kappa-Β ligand (RANKL) decreased of group P. The number of osteocytes was decreased, and the voids was increased. However, cell lacunae were not obvious. The levels of phosphorus, calcium and OCN were increased, and the content of estradiol (E2), OPG and calcitonin (CT) were decreased in serum. In conclusion, the low phosphorus diet can induce layer fatigue syndrome and affect the content of OPG and E2 in serum and the expression of OCN, OPG, RANK and RANKL in femur protein, which leads to the imbalance of bone homeostasis, the thinning of femur cortex bone and the decrease of bone density.

Effects of low dietary phosphorus on tibia quality and metabolism in caged laying hens.

Osteoporosis is a common bone metabolic disease in caged laying hens. This disease affects animal welfare and economic costs. In this study, a model of osteoporosis induced by low dietary phosphorus was established. A total of sixty 22-week-old Roman white laying hens were randomly divided into two groups, including a control group (group C) and a low dietary phosphorus group (group P). The effects of low dietary phosphorus on the endocrine and tibial osteoprotegerin (OPG)/nuclear factor kappa B receptor activating factor ligand (RANKL) signaling pathways of osteoporosis in caged laying hens were analyzed by serology, bone biomechanics, molecular biology and histopathology. The results showed that low dietary phosphorus decreased the production performance, and egg quality of laying hens and increased the contents of serum calcium (Ca), osteocalcin (OCN), alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRACP). The contents of serum phosphorus, calcitonin (CT), OPG and tibial biomechanics index decreased. The bone mineral density (BMD), cortical bone thickness and the expression level of OPG protein in tibia decreased. The expression of OCN, nuclear factor kappa B receptor activating factor (RANK) and RANKL protein increased. Low dietary phosphorus caused thinning and fracture of the bone trabeculae and enlargement of the bone marrow cavity of tibia. Our results suggest that phosphorus may affect bone metabolism by regulating the OPG/RANKL signaling pathway.