Colorectal cancer (CRC) ranks as the third most diagnosed cancer and the second leading cause of cancer-related mortality globally. Hexokinase II, a key rate-limiting enzyme in tumor glycolysis, is an important therapeutic target. In this study, we report that baicalin, a flavonoid derived from Scutellaria baicalensis, acts as a HK2 inhibitor and exerts anti–colorectal cancer activity. In vitro, baicalin markedly suppressed colorectal cancer cell proliferation and colony formation. Molecular docking, molecular dynamics simulations, DARTS, and CETSA suggest an association between baicalin and HK2, while MG132 rescue and HK2 immunoprecipitation indicate that baicalin promotes ubiquitination-associated proteasomal degradation of HK2. Mechanistically, baicalin inhibits HK2, reduces glycolysis, and causes mitochondrial damage, thereby activating the cGAS/STING innate immune signaling pathway and increasing IFN-β production. IFN-β contributes to reshaping the tumor immune microenvironment. In an MC38 syngeneic tumor model, baicalin significantly inhibited tumor growth, reduced HK2 protein levels, activated the cGAS/STING pathway, and promoted a shift in tumor-associated macrophages toward an M1-like polarization state. Collectively, this study uncovers a novel strategy for targeting HK2 to regulate both tumor cell metabolism and the immune microenvironment, providing a potential therapeutic approach for colorectal cancer.

Drynariae Rhizoma has been commonly used as a preventive and therapeutic agent for bone diseases. However, its pharmacological mechanisms have not been fully elucidated. Here, we aimed to investigate the effects of Drynariae Rhizoma in a bilateral ovariectomized rat model and explore the correlation with gut microbiome. We established an ovariectomized rat model, which we treated with different doses of Drynariae Rhizoma (Drynariae Rhizoma-Low, 0.27 g/kg/day; Drynariae Rhizoma-Middle, 0.81 g/kg/day; Drynariae Rhizoma-High, 2.43 g/kg/day) through intragastric administration for 12 weeks. Results showed that Drynariae Rhizoma alleviated body weight, moderated bone microstructure, and promoted the expression of bone formation-related factors in ovariectomized rats, in which Drynariae Rhizoma-High showed the most significant effects among the three doses. Furthermore, the effects of Drynariae Rhizoma on promoting bone formation were correlated to the changes in microbial richness and the restorations of several genera, among which Ruminiclostridium and Ruminococcaceae_UCG_007 were positively correlated with the bone formation-related factors, and both were enriched in the Drynariae Rhizoma-High group as biomarkers. Moreover, CMP-legionaminate biosynthesis I might be a crucial pathway of Drynariae Rhizoma to regulate gut microbiota. The content of serum short-chain fatty acids in the ovariectomized rats were regulated by Drynariae Rhizoma. Our results demonstrate that Drynariae Rhizoma promotes bone formation in ovariectomized rats, and is related to the regulation of the gut microbiota structure.

Osteoporosis (OP) is characterized by impaired bone formation, largely attributed to dysfunctional osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Circulating factors, particularly exosomes acting as natural nanocarriers, play crucial roles in regulating BMSCs function within the bone microenvironment. However, the specific mechanisms by which serum exosomes contribute to osteogenic impairment in OP remain elusive. Serum exosomes were isolated from ovariectomized (OVX) rats and characterized. Their impact on BMSCs osteogenesis was evaluated. Global miRNA sequencing identified dysregulated miRNAs in OVX-derived exosomes. The roles of miR-29a-3p and miR-29c-3p were investigated using gain- and loss-of-function approaches in vitro and in vivo. Bioinformatic analysis and experimental validation identified Ten-Eleven Translocation 3 (TET3) as a direct target. TET3 deficiency was modeled in OVX mice. Transcriptomic analysis, bisulfite sequencing PCR, and chromatin immunoprecipitation sequencing were employed to delineate the mechanism of action of TET3. Exosomes derived from OVX rat serum significantly inhibited osteogenic differentiation of BMSCs. MiRNA sequencing revealed a pronounced downregulation of miR-29a-3p and miR-29c-3p within these exosomes. Functionally, overexpression of miR-29a/29c-3p rescued bone formation defects both in vitro and in vivo, while their inhibition suppressed osteogenesis. Mechanistically, TET3, a key DNA demethylase, was confirmed as a direct target of miR-29a/29c-3p. Crucially, TET3 deficiency in OVX mice stimulated BMSCs osteogenesis and bone remodeling. Further mechanistic dissection demonstrated that TET3 represses osteogenesis by directly increasing DNA methylation at the Sox9 promoter, thereby suppressing Sox9 expression, and concurrently inhibiting the PI3K/AKT signaling pathway. Our study defines a novel exosome-mediated pathway in OP: Deficiency of serum exosome-delivered miR-29a/29c-3p elevates TET3, which epigenetically represses Sox9 via promoter hypermethylation and inhibits PI3K/AKT signaling. This exosome/miR-29/TET3/Sox9 axis unveils promising therapeutic targets for OP intervention, particularly leveraging exosome-based modulation or epigenetic editing.

Postmenopausal osteoporosis, primarily driven by estrogen deficiency, is predominantly mediated through estrogen receptors such as ER alpha. However, the underlying mechanisms necessitate further investigation. In this study, we established an ER alpha-deficient model in rBMSCs to elucidate the role of ER alpha in osteogenic differentiation and miRNA expression profiles. Our findings demonstrate that knockdown of ER alpha inhibits osteogenic differentiation in rBMSCs, resulting in upregulation of 25 miRNAs and downregulation of 184 miRNAs, including a significant increase in the expression of miR-214-3p. Validation using qPCR, Western blotting, and bioinformatics analysis revealed that miR-214-3p negatively regulates osteogenic differentiation via the Wnt/beta-catenin signaling pathway. Furthermore, we explored the potential therapeutic effects of quercetin (QUE) on rBMSCs. CCK8, alkaline phosphatase activity assays, and Alizarin Red staining demonstrated that QUE dose-dependently enhances rBMSCs proliferation, alkaline phosphatase activity, and mineralization within the concentration range of 0.1-1 mu M. Importantly, QUE was found to downregulate miR-214-3p expression and activate the Wnt3a/ beta-catenin signaling pathway. Rescue experiments confirmed that QUE could counteract the inhibitory effects of miR-214-3p on the Wnt3a/beta-catenin signaling pathway. Collectively, our study provides compelling evidence that knockdown of ER alpha inhibits the osteogenic differentiation of rBMSCs by affecting the miRNA expression profile, while QUE can reverse the inhibitory effect exerted by miR-214-3p on the Wnt3a/beta-catenin signaling pathway, thereby offering novel insights into diagnosis, prevention, and treatment strategies for postmenopausal osteoporosis.

Osteoporosis (OP) is a complex bone metabolism disorder disease that affects the skeleton, nervous system, muscles, and multiple tissues. Neuropeptides, which are endogenous substances derived from both bone and brain, play a critical role in maintaining the balance of bone metabolism. This review summarizes research conducted from 1986 to 2024 on the pathological mechanisms of neuropeptides and their receptors in the context of OP. Specifically, the roles of Neuropeptide Y, Vasoactive Intestinal Peptide, Calcitonin Gene-Related Peptide, and Substance P and their receptors in key processes of OP were examined, including their function of bone formation and resorption, osteoblast differentiation, and osteoclast differentiation. Our study showed that these neuropeptides could promote bone formation and inhibit bone resorption, while their receptors in osteocytes exhibit distinct functions, indicating complex regulatory mechanisms that require further investigation. Additionally, we summarize the progress of Traditional Chinese Medicine (TCM) formulae, single TCM herbs, and bioactive compounds derived from TCM in exerting anti-OP effects through neuropeptide modulation. These studies highlight the multi-targeted and multi-mechanistic pharmacological actions of TCM in treating OP. By integrating these findings, we aim to enhance the understanding of neuropeptides’ roles in bone metabolism and to explore the development of neuropeptide-targeted TCM therapies for OP management. This comprehensive perspective highlights the potential of neuropeptides as therapeutic targets, paving the way for innovative approaches to treating OP.

BACKGROUND:Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and a major contributor to cancer-related mortality. This study investigates the role of p21 (RAC1)-activated kinase 6 (PAK6) in LUAD progression, with a focus on its involvement in modulating resistance to ferroptosis. METHODS:GEO datasets were analyzed to identify genes with altered expression in LUAD. Loss-of-function assays were conducted in human LUAD cell lines to assess the effects of PAK6 depletion on cell viability, proliferation, and cell death. Ferroptosis sensitivity was evaluated by measuring levels of ferrous iron (Fe2 +) and malondialdehyde (MDA). The interaction between PAK6 and pumilio RNA-binding family member 1 (PUM1) was assessed using RNA immunoprecipitation and luciferase assays. For in vivo verification, mouse LA795 LUAD cells were implanted into nude mice. RESULTS:Bioinformatics analysis revealed that PAK6 is upregulated in LUAD. Increased immunofluorescence staining and mRNA expression of PAK6 were confirmed in human LUAD cell lines. Loss of PAK6 inhibited the proliferation and migration of LUAD cells in vitro while promoting cell death. However, ferroptosis inhibition reduced cell death. Furthermore, PAK6 silencing elevated Fe2+ and MDA levels, and enhanced the anti-tumor effects of the ferroptosis inducer Erastin. PUM1, which is upregulated in LUAD, binds to PAK6 and stabilizes its RNA. Silencing PUM1 promoted ferroptosis both in vitro and in animal models, an effect that was reversed by artificial restoration of PAK6. CONCLUSION:This study demonstrates that PUM1 enhances the RNA stability of PAK6, thereby contributing to ferroptosis resistance in LUAD cells.

To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.

ETHNOPHARMACOLOGICAL RELEVANCE:Rehmanniae Radix Praeparata (RRP), a widely used traditional Chinese medicine and a processed form of Rehmannia glutinosa, is primarily utilized to supplement kidney function and promote bone health. Clinical evidence suggests that RRP exhibits significant efficacy in the treatment of osteoporosis (OP). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. AIM OF THE STUDY:OP is a systemic skeletal disorder characterized by reduced bone density and quality, leading to an increased risk of fractures. The aim of this study is to evaluate the effectiveness and underlying mechanisms of RRP in treating OP. MATERIALS AND METHODS:Ovariectomized (OVX) rats were administered RRP aqueous extract via gavage for three months. After the treatment period, femoral microstructure and osteogenic protein levels were assessed to evaluate the efficacy of RRP. Serum exosomes (Exos) derived from different groups of rats were isolated and characterized. The levels of miR-29a-3p in serum-derived Exos and femoral tissue were quantified. Subsequently, Exos were co-cultured with rat bone marrow mesenchymal stem cells (rBMSCs) to investigate their role in promoting osteogenic differentiation and explore the molecular mechanisms underlying this process, particularly through the miR-29a-3p/NFIA/Wnt signaling pathway axis. RESULTS:OVX rats exhibited significant bone microdamage. In contrast, the RRP-treated OVX rats showed marked improvements in femoral bone microstructure and increased osteogenic protein expression. MiR-29a-3p levels were elevated in serum-derived Exos from the RRP-treated rats. Furthermore, rBMSCs treated with these Exos displayed an increase in miR-29a-3p expression. Further investigations revealed that miR-29a-3p promoted osteogenesis by inhibiting NFIA expression in both bone tissue and rBMSCs. Overexpression of NFIA reversed the osteogenic effects of miR-29a-3p, confirming NFIA as its direct target and suggesting that miR-29a-3p enhances osteogenesis by inhibiting NFIA. Additionally, NFIA was found to promote the transcription of SFRP1, an inhibitor of the Wnt signaling pathway. Our findings suggest that the RRP aqueous extract increases miR-29a-3p levels in serum Exos, which in turn inhibits NFIA and activates the Wnt signaling pathway, thereby promoting osteogenesis. CONCLUSION:These findings suggest that the RRP aqueous extract improves bone health and mitigates bone microstructural damage caused by OP through the regulation of the miR-29a-3p/NFIA/Wnt signaling pathway axis.

In the original publication [...].

BackgroundFemoral head necrosis is a common orthopedic disease that results in significant physical disability in patients. Early prediction and diagnosis of steroid-induced osteonecrosis of the femoral head (SONFH) are crucial for the prevention and treatment of this condition.MethodsIn this study, initial CT images and clinical data of patients with SONFH, admitted from January 2019 to December 2022, were collected. Patients were grouped as follows: (1) those diagnosed with SONFH at the initial diagnosis (control group), and (2) those with high-risk factors but no symptoms at first diagnosis, who developed SONFH two years later (experimental group). CT imaging histological features, clinical characteristics, and transcriptome screening for differentially expressed genes, pathway enrichment, and immune infiltration analyses were performed.ResultsSignificant differences were found in triglyceride (TG) levels between the training and validation groups. Age, sex, alkaline phosphatase (ALP), and hemoglobin levels differed between the training and internal validation groups, while HDL and red blood cell counts varied between the training and external validation groups. Univariate analysis showed that age, TG, HDL, and Radiomics scores influenced SONFH, while multivariate analysis revealed TG, HDL, and Radiomics scores were closely related to SONFH. Transcriptomic analysis showed associations with sphingolipid and adipocyte signaling pathways, along with immune cell involvement, linking SONFH to lipid metabolism and atherosclerosis.ConclusionsThese findings indicate a significant association between steroid-induced osteonecrosis of the femoral head and age, with TG and HDL serving as indicators of lipid metabolism closely correlated with the occurrence of SONFH. Radiomics scores were also found to correlate with SONFH occurrence, supported by transcriptomic and CT imaging findings. However, this study has limitations, including its retrospective design and a relatively limited sample size, which may impact the generalizability of the results. Further prospective studies with larger, more diverse populations are needed to validate and enhance the predictive model.

Tumor cells can promote angiogenesis by secreting extracellular vesicles (EVs). Meanwhile, tumor-derived EVs can carry long non-coding RNAs to activate pro-angiogenic signaling in endothelial cells. Here, we investigated the role of long non-coding RNA MCM3AP-AS1 carried by cervical cancer (CC) cell-derived EVs in the angiogenesis and the resultant tumor growth in CC, as well as the potential molecular mechanisms. LncRNAs significantly expressed in CC cell-derived EVs and CC were screened, followed by prediction of downstream target genes. EVs were isolated from HcerEpic and CaSki cell supernatants, followed by identification. The expression of MCM3AP-AS1 in CC was analyzed and its interaction with miR-93-p21 was confirmed. Following co-culture system, the role of MCM3AP-AS1 carried by EVs in HUVEC angiogenic ability, CC cell invasion and migration in vitro along with angiogenesis and tumorigenicity in vivo was assayed. MCM3AP-AS1 was overexpressed in CC cell-derived EVs as well as in CC tissues and cell lines. Cervical cancer cell-derived EVs could transfer MCM3AP-AS1 into HUVECs where MCM3AP-AS1 competitively bound to miR-93 and upregulate the expression of the miR-93 target p21 gene. Thus, MCM3AP-AS1 promoted angiogenesis of HUVECs. In the similar manner, MCM3AP-AS1 enhanced CC cell malignant properties. In nude mice, EVs-MCM3AP-AS1 induced angiogenesis and tumor growth. Overall, this study reveals that CC cell-derived EVs may transport MCM3AP-AS1 to promote angiogenesis and tumor growth in CC.

Xian-Ling-Gu-Bao capsule (XLGB) is a widely prescribed traditional Chinese medicine used for the treatment of osteoporosis. However, it significantly elevates levels of serum estrogens. Here we aimed to assess the dominant contributors of sulfotransferase (SULT) enzymes to the sulfation of estrogens and identify the effective inhibitors of this pathway in XLGB. First, estrone, 17β-estradiol, and estriol underwent sulfation in human liver S9 extracts. Phenotyping reactions and enzyme kinetics assays revealed that SULT1A1, 1A2, 1A3, 1C4, 1E1, and 2A1 all participated in estrogen sulfation, with SULT1E1 and 1A1 as the most important contributors. The incubation system for these two active enzymes were optimized with Tris-HCl buffer, DL-Dithiothreitol (DTT), MgCl2, adenosine 3'-phosphate 5'-phosphosulfate (PAPS), protein concentration, and incubation time. Then, 29 compounds in XLGB were selected to investigate their inhibitory effects and mechanisms against SULT1E1 and 1A1 through kinetic modelling. Moreover, in silico molecular docking was used to validate the obtained results. And finally, the prenylated flavonoids (isobavachin, neobavaisoflavone, etc.) from Psoralea corylifolia L., prenylated flavanols (icariside II) from Epimedium brevicornu Maxim., tanshinones (dihydrotanshinone, tanshinone II-A,) from Salvia miltiorrhiza Bge., and others (corylifol A, corylin) were identified as the most potent inhibitors of estrogen sulfation. Taken together, these findings provide insights into the understanding regioselectivity of estrogen sulfation and identify the effective components of XLGB responsible for the promotion of estrogen levels.

Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 3'UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway. (C) 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

As a serious and elusive syndrome caused by infection, sepsis causes a high rate of mortality around the world. Our investigation aims at exploring the role and possible mechanism of specificity protein-1 (SP1) in the development of sepsis. A mouse model of sepsis was established by cecal ligation perforation, and a cellular model was stimulated by lipopolysaccharide (LPS), followed by determination of the SP1 expression. It was determined that SP1 was poorly expressed in the intestinal tissues of septic mice and LPS-treated cells. Next, we examined the interactions among SP1, histone deacetylase 4 (HDAC4), and high mobility group box 1 (HMGB1) and found that SP1 bound to the HDAC4 promoter to upregulate its expression, thereby promoting the deacetylation of HMGB1. Meanwhile, gain- or loss-of-function approaches were applied to evaluate the intestinal barrier dysfunction, oxidative stress, and inflammatory response. Overexpression of SP1 or underexpression of HMGB1 was observed to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory injury. Collectively, these experimental data provide evidence reporting that SP1 could promote the HDAC4-mediated HMGB1 deacetylation to reduce intestinal barrier dysfunction, oxidative stress, and inflammatory response induced by sepsis, providing a novel therapeutic target for sepsis prevention and treatment.

The dream of human beings for long living has stimulated the rapid development of biomedical and healthcare equipment. However, conventional biomedical and healthcare devices have shortcomings such as short service life, large equipment size, and high potential safety hazards. Indeed, the power supply for conventional implantable device remains predominantly batteries. The emerging nanogenerators, which harvest micro/nanomechanical energy and thermal energy from human beings and convert into electrical energy, provide an ideal solution for self‐powering of biomedical devices. The combination of nanogenerators and biomedicine has been accelerating the development of self‐powered biomedical equipment. This article first introduces the operating principle of nanogenerators and then reviews the progress of nanogenerators in biomedical applications, including power supply, smart sensing, and effective treatment. Besides, the microbial disinfection and biodegradation performances of nanogenerators have been updated. Next, the protection devices have been discussed such as face mask with air filtering function together with real‐time monitoring of human health from the respiration and heat emission. Besides, the nanogenerator devices have been categorized by the types of mechanical energy from human beings, such as the body movement, tissue and organ activities, energy from chemical reactions, and gravitational potential energy. Eventually, the challenges and future opportunities in the applications of nanogenerators are delivered in the conclusive remarks. image

ScopeGlycine is commonly used as an additive in bone health supplements, the activity and differentiation of bone mesenchymal stem cells (BMSCs) are essential to bone metabolism, but the effect of Glycine on bone metabolism and specific mechanism are not fully clarified.Methods and resultsThe ovariectomized rats to evaluate the effects of Glycine on bone quality and quantity is constructed; then used an ER signaling inhibitor (ICI182780) and an ERα deficient BMSCs to explore how Glycine mediated ERα regulating the osteogenic and adipogenic differentiation of BMSCs; furthermore, an autodock analysis is used to assess the affinity of Glycine and ERα. The results show that Glycine significantly moderated bone mass and bone microstructure in ovariectomized rats; Glycine stimulates the osteogenic differentiation and attenuates the adipogenic differentiation in OVX rats and BMSCs, and these effects could be abolished by ICI 182780; further docking experiment showes that Glycine and ERα have a stronger affinity, and finally proves that the impact of Glycine could be blocked by ERα.ConclusionGlycine stimulates osteogenesis and attenuates adipogenesis in ovariectomized rats, which process may involve in ERα mediated ER signaling pathway.

Excessive salt intake can induce a variety of diseases, such as hypertension, cardiovascular disease, kidney disease and so on,it is also one of the factors promoting bone resorption. The mechanism of osteoporosis -induced exacerbations of high salt diet is not well-defined. In this study, we used ovariectomized 6-month-old Sprague Dawley rats to construct a high bone turnover model, and then administrated with high sodium chlo-ride diet (2.0% w/w NaCl, 8.0% w/w NaCl) for 12 weeks to observe the effect of high salt diet on bone meta-bolism. The results showed that high salt diet could lead to the destruction of bone microstructure, promote the excretion of urinary calcium and phosphorus and accelerate the bone turnover, as well as cause the pathologic structural abnormalities in renal tubular. At the same time, it was accompanied by the up-regulated expression of the epithelial sodium channel (ENaC alpha), voltage-gated chloride channels (ClC)-3 and the down-regulated expression of Na-Cl cotransporter (NCC), sodium calcium exchanger (NCX1) in femoral tissue and renal tu-bules. These findings confirm that high salt diet can destroy the microstructure of bone by increasing bone resorption and affect some ion channels of bone tissue and renal tubule in ovariectomized rats.