Biochemistry and Biophysics Reports最新文献

{"title":"Generation of bone-specific lysyl hydroxylase 2 knockout mice and their phenotypes","authors":"Kenta Tsuneizumi ,&nbsp;Atsushi Kasamatsu ,&nbsp;Tomoaki Saito ,&nbsp;Reo Fukushima ,&nbsp;Yuki Taga ,&nbsp;Kazunori Mizuno ,&nbsp;Masataka Sunohara ,&nbsp;Katsuhiro Uzawa ,&nbsp;Mitsuo Yamauchi","doi":"10.1016/j.bbrep.2024.101790","DOIUrl":"10.1016/j.bbrep.2024.101790","url":null,"abstract":"<div><p>Lysyl hydroxylase 2 (LH2) catalyzes the hydroxylation of lysine residues in the telopeptides of type I collagen. This modification is critical for the formation of stable hydroxylysine-aldehyde derived collagen cross-links, thus, for the stability of collagen fibrils. Though dysfunction of LH2 causes Bruck syndrome, recessive osteogenesis imperfecta with joint contracture, the molecular mechanisms by which LH2 affects bone formation are still not well understood. Since the <em>Plod2</em> knockout mice are embryonically lethal, we generated bone-specific LH2 conditional knockout mice (bsLH2-cKO) using the osteocalcin-Cre/loxP system, and evaluated phenotypes of femurs. LH2 mRNA and protein levels assessed by qPCR, immunohistochemistry and Data Independent Acquisition proteomics were all markedly low in bsLH2-cKO femurs when compared to controls. Lysine hydroxylation of both carboxy- and amino-terminal telopeptides of an α1(I) chain were significantly diminished resulting in reduction of the hydroxylysine-aldehyde derived cross-links. The collagen fibrils in bsLH2-cKO appeared to be thicker, often fused and irregular when compared to controls. In addition, bone mineral density and mechanical properties of bsLH2-cKO femurs were significantly impaired. Taken together, these data demonstrate that LH2-catalyzed modification and consequent cross-linking of collagen are critical for proper bone formation and mechanical strength.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101790"},"PeriodicalIF":2.3,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001547/pdfft?md5=068bb6e892eaa109df26a3d1dd669388&pid=1-s2.0-S2405580824001547-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterologous expression, characterization, and application of recombinant thermostable α-amylase from Geobacillus sp. DS3 for porous starch production","authors":"Dina Clarissa Kurniawan ,&nbsp;Muhammad Saifur Rohman ,&nbsp;Lucia Dhiantika Witasari","doi":"10.1016/j.bbrep.2024.101784","DOIUrl":"10.1016/j.bbrep.2024.101784","url":null,"abstract":"<div><p>Novel <em>Geobacillus</em> sp. DS3, isolated from the Sikidang Crater in Dieng, exhibits promising characteristics for industrial applications, particularly in thermostable α-amylase production. Recombinant technology was used to express thermostable α-amylase in <em>E. coli</em> BL21(DE3) to overcome high-temperature production challenges. The study aimed to express, purify, characterize, and explore potential applications of this novel enzyme. The enzyme was successfully expressed in <em>E. coli</em> BL21(DE3) at 18 °C for 20 h with 0.5 mM IPTG induction. Purification with Ni-NTA column yielded 69.23 % from the initial crude enzyme, with a 3.6-fold increase in specific activity. The enzyme has a molecular weight of ±70 kDa (±58 kDa enzyme+11 kDa SUMO protein). It exhibited activity over a wide temperature range (30–90 °C) and pH range (6–8), with optimal activity at 70 °C and pH 6 with great stability at 60 °C. Kinetic analysis revealed Km and Vmax values of 324.03 mg/ml and 36.5 U/mg, respectively, with dextrin as the preferred substrate without cofactor addition. As a metalloenzyme, it showed the best activity in the presence of Ca²⁺. The enzyme was used for porous starch production and successfully immobilized with chitosan, exhibiting improved thermal stability. After the fourth reuse, the immobilized enzyme maintained 62 % activity compared to the initial immobilization.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101784"},"PeriodicalIF":2.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001481/pdfft?md5=76db7106b21992589630b0f9dbc7f5e8&pid=1-s2.0-S2405580824001481-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141638226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of opsin and visual cycle-related enzymes in fetal rat skin keratinocytes and cellular response to blue light","authors":"Hiroyuki Yamamoto ,&nbsp;Momo Okada ,&nbsp;Yoshikazu Sawaguchi ,&nbsp;Toshiyuki Yamada","doi":"10.1016/j.bbrep.2024.101789","DOIUrl":"10.1016/j.bbrep.2024.101789","url":null,"abstract":"<div><p>The mechanism by which the skin, a non-visual tissue, responds to light remains unknown. To date, opsin expression has been demonstrated in keratinocytes, melanocytes, and fibroblasts, all of which are skin-derived cells. In this study, we examined whether the visual cycle, by which opsin activity is maintained, is present in skin keratinocytes. We also identified the wavelengths of light to which opsin in keratinocytes responds and explored their effects on skin keratinocytes. The fetal rat skin keratinocytes used in this study expressed OPN2, 3, and 5 in addition to enzymes involved in the visual cycle, and all-<em>trans</em>-retinal, which is produced by exposure to light, was reconverted to 11-<em>cis</em>-retinal, resulting in opsin activation. Using the production of all-<em>trans</em>-retinal after light exposure as an indicator, we discovered that keratinocytes responded to light at 450 nm. Furthermore, actin alpha cardiac muscle 1 expression in keratinocytes was enhanced and cell migration was suppressed by exposure to light at these wavelengths. These results indicate that keratinocytes express various opsins and have a visual cycle that keeps opsin active. Moreover, keratinocytes were shown to respond to the blue/UV region of the light spectrum, suggesting that opsin plays a role in the light response of the skin.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101789"},"PeriodicalIF":2.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001535/pdfft?md5=bcccf11616eca1e6d354ff987fc1a0d2&pid=1-s2.0-S2405580824001535-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the tail current of Channelrhodopsin-2 variants","authors":"TiShang Zheng,&nbsp;HengQi Wei,&nbsp;CongJian Zhao","doi":"10.1016/j.bbrep.2024.101787","DOIUrl":"10.1016/j.bbrep.2024.101787","url":null,"abstract":"<div><p>Our study focused on specific ChR2 variants, particularly those with the Step function Opsins (SFO) mutation at the D156-C128 gate. These are widely used in optogenetics due to their heightened sensitivity to light and bi-stable prolonged activation. However, in some ChR2 variants, specifically D156 mutants, a tail current occurs when continuous light exposure is stopped. We specifically examined the D156H-T159S ChR2 variant, which demonstrated a tail current that was somewhat responsive to light and voltage, with a single-channel current of around 9fA, similar to wt-ChR2 as determined by stationary noise analysis. To further investigate, we used nonstationary noise analysis in cell-attached patching mode, which revealed that the tail current's single-channel current falls within the same range as the peak current, albeit with mild contamination from adaptation and desensitization. This finding strongly supports the notion that a portion of the ChR2 molecules open or re-open at the end of illumination, leading to further membrane depolarization.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101787"},"PeriodicalIF":2.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001511/pdfft?md5=f285b9b1299fe61249d13001ef451776&pid=1-s2.0-S2405580824001511-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141630199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico and ADMET molecular analysis targeted to discover novel anti-inflammatory drug candidates as COX-2 inhibitors from specific metabolites of Diospyros batokana (Ebenaceae)","authors":"Bitwell Chibuye ,&nbsp;Indra Sen Singh ,&nbsp;Luke Chimuka ,&nbsp;Kenneth Kakoma Maseka","doi":"10.1016/j.bbrep.2024.101758","DOIUrl":"https://doi.org/10.1016/j.bbrep.2024.101758","url":null,"abstract":"<div><p><em>Diospyros batokana</em> (Ebenaceae) is a valuable medicinal plant that grows in the wild in Zambia. The aqua crude plant extract is valuable in treating oxidative stress and microbes-related diseases. In this study, bioactive metabolites from the leaf of the plant were tentatively identified using ultra-high-pressure liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS). Raw LCMS data were processed using MZmine3.6. Pyrenophorol, N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl]-2,2-diphenylacetamide, losartan, and isoarthonin, (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide were among the many metabolites identified from the plant studied using LCMS-MZmine 3.6. Furthermore, in silico anti-inflammatory molecular docking was applied to the five (5) metabolites with the aim of predicting the ability of the metabolites to inhibit the COX-2 enzyme. The docking simulation for the five metabolites was executed using the Auto-dock tools. The lowest binding energy of the complexes was visualized using Discovery Studio, 2021 Client l molecular viewer. Pyrenophorol, (N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl] −2,2-diphenylacetamide) and losartan were found to provide the lowest binding energy to COX-2 compared to the standard anti-inflammatory drug, diclofenac. Furthermore, binding affinities, inhibition constants, and ligand efficiencies demonstrated that pyrenophorol, N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl]-2,2-diphenylacetamide, losartan, isoarthonin and (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide could be useful as anti-inflammatory drug candidates supporting the traditional uses of <em>D. batokana</em>. However, the bioavailability radar and physicochemical properties only predict losartan, pyrenophorol, and (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide to be bioavailable and suitable drug candidates. In silico and ADMET analysis, shows that the five metabolites could be used as anti-inflammatory drugs comparable to the standard drugs, diclofenac and ibuprofen. However, in vitro and in vivo studies are needed to further support our findings.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101758"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001225/pdfft?md5=d795094e8bcfcdd46eb09854df302876&pid=1-s2.0-S2405580824001225-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of lipid-translocating exporter family proteins in determination of myriocin sensitivity in budding yeast","authors":"Takahiro Kawaguchi ,&nbsp;Yohei Ishibashi ,&nbsp;Momoko Matsuzaki ,&nbsp;Satomi Yamagata ,&nbsp;Motohiro Tani","doi":"10.1016/j.bbrep.2024.101785","DOIUrl":"https://doi.org/10.1016/j.bbrep.2024.101785","url":null,"abstract":"<div><p>Myriocin is an inhibitor of serine palmitoyltransferase involved in the initial biosynthetic step for sphingolipids, and causes potent growth inhibition in eukaryotic cells. In budding yeast, Rsb1, Rta1, Pug1, and Ylr046c are known as the Lipid-Translocating Exporter (LTE) family and believed to contribute to export of various cytotoxic lipophilic compounds. It was reported that Rsb1 is a transporter responsible for export of intracellularly accumulated long-chain bases, which alleviate the cytotoxicity. In this study, it was found that LTE family genes are involved in determination of myriocin sensitivity in yeast. Analyses of effects of deletion and overexpression of LTE family genes suggested that all LTEs contribute to suppression of cytotoxicity of myriocin. It was confirmed that <em>RSB1</em> overexpression suppressed reduction in complex sphingolipid levels caused by myriocin treatment, possibly exporting myriocin to outside of the cell. These results suggested that LTE family genes function as a defense mechanism against myriocin.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101785"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001493/pdfft?md5=0bb104b31ac7a2081220ac064553e280&pid=1-s2.0-S2405580824001493-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A non-invasive screening method using Caenorhabditis elegans for early detection of multiple cancer types: A prospective clinical study","authors":"Hideyuki Hatakeyama,&nbsp;Masayo Morishita,&nbsp;Aya Hasan Alshammari,&nbsp;Umbhorn Ungkulpasvich,&nbsp;Junichi Yamaguchi,&nbsp;Takaaki Hirotsu,&nbsp;Eric di Luccio","doi":"10.1016/j.bbrep.2024.101778","DOIUrl":"https://doi.org/10.1016/j.bbrep.2024.101778","url":null,"abstract":"<div><p>Cancer is the second leading cause of death worldwide, according to the World Health Organization, surpassed only by cardiovascular diseases. Early identification and intervention can significantly improve outcomes. However, finding a universal, non-invasive, economical, and precise method for early cancer detection remains a significant challenge. This study explores the efficacy of an innovative cancer detection test, N-NOSE, leveraging a <em>Caenorhabditis elegans</em> olfactory assay on urine samples across a diverse patient group exceeding 1600 individuals diagnosed with various cancers, with samples from the Shikoku Cancer Center (Ehime, Japan) under approved ethical standards. Current cancer screening techniques often require invasive procedures, can be painful or complex, with poor performance, and might be prohibitively costly, limiting accessibility for many. N-NOSE addresses these challenges head-on by offering a test based on urine analysis, eliminating the need for invasive methods, and being more affordable with higher performance at early stages than extensive blood tests or comprehensive body scans for cancer detection. In this study, N-NOSE demonstrated a capability to accurately identify upwards of 20 cancer types, achieving detection sensitivities between 60 and 90 %, including initial-stage cancers. The findings robustly advocate for N-NOSE's potential as a revolutionary, cost-effective, and minimally invasive strategy for broad-spectrum early cancer detection. It is also particularly significant in low- and middle-income countries with limited access to advanced cancer diagnostic methods, which may contribute to the improved outcome of affected individuals.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101778"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001420/pdfft?md5=18e443a3dfdb619c80d3262d64c2803d&pid=1-s2.0-S2405580824001420-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of hub lncRNAs correlated with tetralogy of fallot based on weighted gene co-expression network analysis","authors":"Ye Ding ,&nbsp;Chun Zhu","doi":"10.1016/j.bbrep.2024.101786","DOIUrl":"https://doi.org/10.1016/j.bbrep.2024.101786","url":null,"abstract":"<div><p>The most prevalent cyanotic congenital heart disease, Tetralogy of Fallot (TOF), has an unknown etiology. Long-stranded non-coding RNAs (lncRNAs) have been linked to cardiac development and congenital heart disease, as evidenced by an increasing number of studies; nevertheless, additional research is necessary to fully understand the function that TOF-related lncRNAs play in the condition. This study constructed lncRNA-mRNA co-expression networks, performed functional enrichment analysis, and screened hub lncRNAs using Weighted Gene Co-expression Network Analysis (WGCNA) using the Gene Expression Omnibus dataset GSE36761. Ten hub lncRNAs, including IRF1-AS1, AC012360.6, HLA-F-AS1, RP1-253P7.4, NPTN-IT1, RP11–166P13.4, RP5-1183I21.2, SNHG14, CH17-98J9.1, and RP11–894P9.1, were identified by WGCNA analysis as potentially significant contributors to the development of TOF. Based on functional enrichment analysis, lncRNA mainly contributes to TOF by altering gene splicing patterns. New insights on the mechanism underlying TOF occurrence are provided by identifying hub lncRNAs associated with the disease and analyzing their regulatory networks.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101786"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S240558082400150X/pdfft?md5=92740457cd42c98d22767817dd688652&pid=1-s2.0-S240558082400150X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cxcr4a regulates heart progenitor development and cardiac rhythm in zebrafish","authors":"Bingyu Chen ,&nbsp;Qin Ran ,&nbsp;Xin Chen ,&nbsp;Zhilin Deng ,&nbsp;Rong Zhou ,&nbsp;Yu Zhang ,&nbsp;Min Liu ,&nbsp;Botong Li ,&nbsp;Shuying Huang ,&nbsp;Peijian Wang ,&nbsp;Sizhou Huang","doi":"10.1016/j.bbrep.2024.101782","DOIUrl":"https://doi.org/10.1016/j.bbrep.2024.101782","url":null,"abstract":"<div><p><em>Cxcr4a</em> is involved in multiple organ development including coronary vasculature formation and heart left-right (LR) patterning, whether it is involved in heart progenitor determination and cardiac rhythm regulation is not addressed. Here we showed that in <em>cxcr4a</em> mutants, from 2 days post fertilization (dpf) to 4dpf the embryos transiently displayed pericardial edema and increased cardiac rhythm. While from 5dpf, the heart phenotype disappeared. Detailed analysis demonstrated that, at 36hpf and 48hpf, even though there was no distinct difference in the heart size between <em>cxcr4a</em> mutants and controls, the expression of <em>myl7</em> was decreased. Further data showed that, the heart progenitors were decreased at 18SS(Somite Stage). Mechanically, RNA-seq, RT-qPCR and <em>in situ</em> experiments showed that the retinoic acid (RA) signaling was upregulated, and the up-regulation of RA signaling may mediate the role of <em>cxcr4a</em> in regulating heart progenitor development. In addition, we also identified that low dose of RA treatment accelerated the cardiac rhythm, being similar to that in <em>cxcr4a</em> mutants. Decreasing RA signaling partially restored the rapid cardiac rhythm in <em>cxcr4a</em> mutants, implying the possibility that RA signaling partially mediates the role of <em>cxcr4a</em> in regulating cardiac rhythm. In conclusion, our study identified <em>cxcr4a</em> simultaneously regulates heart progenitor determination and cardiac rhythm.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101782"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001468/pdfft?md5=47c49b1b9dfb8ca79c239401dbcee704&pid=1-s2.0-S2405580824001468-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro osteoclast differentiation enhanced by hepatocyte supernatants from high-fat diet mice","authors":"Yan Wang ,&nbsp;Fangli Zhou ,&nbsp;Siyi Shu ,&nbsp;Yunhong Wu ,&nbsp;Haoming Tian ,&nbsp;Yujue Li ,&nbsp;Xiang Chen","doi":"10.1016/j.bbrep.2024.101788","DOIUrl":"https://doi.org/10.1016/j.bbrep.2024.101788","url":null,"abstract":"<div><p>Non-alcoholic fatty liver disease (NAFLD) is associated with abnormal bone metabolism, potentially mediated by elevated levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-ɑ) and interleukin 6 (IL-6). This study aims to investigate the direct regulatory effects of liver tissues on osteoblast and osteoclast functions <em>in vitro</em>, focusing on the liver-bone axis in NAFLD. Twelve-week-old C57BL/6 mice were fed either a control diet or a high-fat diet (HFD) for 12 weeks. Bone structural parameters were assessed using microCT. Primary hepatocyte cultures were established from control and HFD-fed C57BL/6 mice, as well as IL-6^−/− and TNF-α^−/− mice. The supernatants from these hepatocyte cultures were used to induce differentiation in bone marrow cell-derived osteoblasts and osteoclasts <em>in vitro</em>. Results showed that mice on a HFD exhibited increased lipid infiltration in liver and bone marrow tissues, alongside reduced bone mass. Moreover, the supernatants from hepatocyte cultures from mice on a HFD displayed elevated TNF-α and IL-6 levels. These supernatants, particularly those derived from HFD-fed and IL-6^−/− mice, significantly enhanced osteoclast differentiation <em>in vitro</em>. In contrast, supernatants from TNF-α^−/− mice did not significantly affect osteoblast or osteoclast differentiation <em>in vitro</em>. In conclusions, this current study suggested that fatty liver tissues may negatively impact bone metabolism. Additionally, knockout of <em>TNF-α</em> and <em>IL-6</em> genes revealed distinct influence on osteoblast and osteoclast functions, highlighting the complex interplay between live pathology and bone health.</p></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"39 ","pages":"Article 101788"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001523/pdfft?md5=bc834b6e6934f34c1527cf2a298c3e29&pid=1-s2.0-S2405580824001523-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}