Umeå University's logo

umu.sePublications
Change search
Link to record
Permanent link

Direct link
Alternative names
Publications (10 of 225) Show all publications
Liu, L., Liu, H., Meng, P., Zhang, Y., Zhang, F., Jia, Y., . . . Guo, X. (2024). Involvement of yes-associated protein 1 activation in the matrix degradation of human-induced-pluripotent-stem-cell-derived chondrocytes induced by T-2 toxin and deoxynivalenol alone and in combination. International Journal of Molecular Sciences, 25(2), Article ID 878.
Open this publication in new window or tab >>Involvement of yes-associated protein 1 activation in the matrix degradation of human-induced-pluripotent-stem-cell-derived chondrocytes induced by T-2 toxin and deoxynivalenol alone and in combination
Show others...
2024 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, no 2, article id 878Article in journal (Refereed) Published
Abstract [en]

T-2 toxin and deoxynivalenol (DON) are two prevalent mycotoxins that cause cartilage damage in Kashin-Beck disease (KBD). Cartilage extracellular matrix (ECM) degradation in chondrocytes is a significant pathological feature of KBD. It has been shown that the Hippo pathway is involved in cartilage ECM degradation. This study aimed to examine the effect of YAP, a major regulator of the Hippo pathway, on the ECM degradation in the hiPS-derived chondrocytes (hiPS-Ch) model of KBD. The hiPS-Ch injury models were established via treatment with T-2 toxin/DON alone or in combination. We found that T-2 toxin and DON inhibited the proliferation of hiPS-Ch in a dose-dependent manner; significantly increased the levels of YAP, SOX9, and MMP13; and decreased the levels of COL2A1 and ACAN (all p values < 0.05). Immunofluorescence revealed that YAP was primarily located in the nuclei of hiPS-Ch, and its expression level increased with toxin concentrations. The inhibition of YAP resulted in the dysregulated expression of chondrogenic markers (all p values < 0.05). These findings suggest that T-2 toxin and DON may inhibit the proliferation of, and induce the ECM degradation, of hiPS-Ch mediated by YAP, providing further insight into the cellular and molecular mechanisms contributing to cartilage damage caused by toxins.

Place, publisher, year, edition, pages
MDPI, 2024
Keywords
Deoxynivalenol, Kashin–Beck disease, T-2 toxin, YAP, hiPSCs
National Category
Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell Biology
Research subject
cell research; Medical Cell Biology; Toxicology
Identifiers
urn:nbn:se:umu:diva-219960 (URN)10.3390/ijms25020878 (DOI)001152922800001 ()38255951 (PubMedID)2-s2.0-85183253930 (Scopus ID)
Available from: 2024-01-25 Created: 2024-01-25 Last updated: 2024-03-18Bibliographically approved
Fan, Y., Bian, X., Meng, X., Li, L., Fu, L., Zhang, Y., . . . Sun, S. (2024). Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration. Annals of the Rheumatic Diseases
Open this publication in new window or tab >>Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration
Show others...
2024 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060Article in journal (Refereed) Epub ahead of print
Abstract [en]

OBJECTIVES: Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations.

METHODS: Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies.

RESULTS: We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype.

CONCLUSIONS: Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2024
Keywords
chondrocytes, inflammation, osteoarthritis, knee, single cell RNA-seq
National Category
Rheumatology and Autoimmunity Orthopaedics Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell Biology Biochemistry and Molecular Biology
Research subject
Biochemistry; cell research; Medical Biochemistry; Medical Cell Biology; Orthopaedics; rheumatology
Identifiers
urn:nbn:se:umu:diva-221149 (URN)10.1136/ard-2023-224420 (DOI)38325908 (PubMedID)2-s2.0-85184771148 (Scopus ID)
Available from: 2024-02-20 Created: 2024-02-20 Last updated: 2024-02-20
Wang, S., Wang, Y., Li, X., Yuan, L., Guo, X. & Lammi, M. (2023). ATAC-seq reveals the roles of chromatin accessibility in the chondrocytes of Kashin-Beck disease compared with primary osteoarthritis. Frontiers in Genetics, 14, Article ID 1169417.
Open this publication in new window or tab >>ATAC-seq reveals the roles of chromatin accessibility in the chondrocytes of Kashin-Beck disease compared with primary osteoarthritis
Show others...
2023 (English)In: Frontiers in Genetics, ISSN 1664-8021, Vol. 14, article id 1169417Article in journal (Refereed) Published
Abstract [en]

Objective: This study aimed to investigate the roles of accessible chromatin in understanding the different pathogeneses between Kashin-Beck disease (KBD) and primary osteoarthritis (OA).

Methods: Articular cartilages of KBD and OA patients were collected, and after tissue digestion, primary chondrocytes were cultured in vitro. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) was performed to compare the accessible chromatin differences of chondrocytes between KBD and OA groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were executed for the promoter genes. Then, the IntAct online database was used to generate networks of significant genes. Finally, we overlapped the analysis of differentially accessible region (DAR)-associated genes and differentially expressed genes (DEGs) obtained from whole-genomic microarray.

Results: We obtained 2,751 total DARs, which contained 1,985 loss and 856 gain DARs and belonged to 11 location distributions. We obtained 218 motifs associated with loss DARs, 71 motifs associated with gain DARs, 30 motif enrichments of loss DARs, and 30 motif enrichments of gain DARs. In total, 1,749 genes are associated with loss DARs, and 826 genes are associated with gain DARs. Among them, 210 promoter genes are associated with loss DARs, and 112 promoter genes are associated with gain DARs. We obtained 15 terms of GO enrichment and 5 terms of KEGG pathway enrichment from loss DAR promoter genes, and 15 terms of GO enrichment and 3 terms of KEGG pathway enrichment from gain DAR promoter genes. We obtained CAPN6 and other 2 overlap genes from loss DARs-vs-down DEGs, AMOTL1 from gain DARs-vs-down DEGs, EBF3 and other 12 overlap genes from loss DARs-vs-up DEGs, and ADARB1 and other 10 overlap genes from 101 gain DARs-vs-up DEGs. These overlap genes were built into 4 gene interaction networks.

Conclusion: FGF7, GPD1L, NFIB, RUNX2, and VCAM1 were the overlapped genes from the DAR-associated genes and DEGs. These genes were associated with the abnormal chondrocyte function, which may play crucial roles in different processes between KBD and OA in the way of accessible chromatin.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
ATAC-seq, Kashin–Beck disease, cartilage, chondrocyte, osteoarthritis
National Category
Rheumatology and Autoimmunity Cell and Molecular Biology
Research subject
cell research; rheumatology
Identifiers
urn:nbn:se:umu:diva-209508 (URN)10.3389/fgene.2023.1169417 (DOI)000999642100001 ()37287534 (PubMedID)2-s2.0-85161086366 (Scopus ID)
Available from: 2023-06-10 Created: 2023-06-10 Last updated: 2023-06-15Bibliographically approved
Lammi, M. J., Wang, X. & Ning, Y. (2023). Editorial: Genetic and environmental roles in bone and joint diseases. Frontiers in Genetics, 14, Article ID 1177191.
Open this publication in new window or tab >>Editorial: Genetic and environmental roles in bone and joint diseases
2023 (English)In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 14, article id 1177191Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
bone, cartilage, environment, genetics, joint
National Category
Orthopaedics Rheumatology and Autoimmunity Genetics
Research subject
cell research; Genetics; Medical Cell Biology; rheumatology
Identifiers
urn:nbn:se:umu:diva-208106 (URN)10.3389/fgene.2023.1177191 (DOI)000982088800001 ()37152981 (PubMedID)2-s2.0-85158165896 (Scopus ID)
Available from: 2023-05-09 Created: 2023-05-09 Last updated: 2023-06-02Bibliographically approved
Ning, Y., Minhan, H., Yi, G., Ruitian, H., Ke, X., Sijie, C., . . . Xi, W. (2022). Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China. Arthritis Research & Therapy, 24(1), Article ID 129.
Open this publication in new window or tab >>Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China
Show others...
2022 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 24, no 1, article id 129Article in journal (Refereed) Published
Abstract [en]

Background: Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients.

Methods: Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed.

Results: The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella, Citrobacter, Flavonifractor, g__Lachnospiraceae_UCG-004, and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia, and Holdemanella. The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74, Streptococcus_parasanguinis, and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri, Prevotella_sp._CAG:386, and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing.

Conclusion: Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.

Place, publisher, year, edition, pages
BioMed Central, 2022
Keywords
Osteoarthritis, Kashin-Beck disease, 16S sequencing, Metagenomic sequencing, Microbiota
National Category
Clinical Medicine Rheumatology and Autoimmunity Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Microbiology
Research subject
Microbiology; molecular biotechnology (dept of cell- and molecular biology); rheumatology
Identifiers
urn:nbn:se:umu:diva-195579 (URN)10.1186/s13075-022-02819-5 (DOI)000805592000003 ()2-s2.0-85130915740 (Scopus ID)
Available from: 2022-05-31 Created: 2022-05-31 Last updated: 2023-09-05Bibliographically approved
Ning, Y., Hu, M., Diao, J., Gong, Y., Huang, R., Chen, S., . . . Guo, X. (2022). Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy. Frontiers in Genetics, 12, Article ID 773534.
Open this publication in new window or tab >>Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy
Show others...
2022 (English)In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 12, article id 773534Article in journal (Refereed) Published
Abstract [en]

The mechanism of environmental factors in Kashin-Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin-responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin-responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022
Keywords
Kashin–Beck disease, T-2 toxin, chondrocyte damage, selenium, single nucleotide polymorphism
National Category
Orthopaedics Cell and Molecular Biology Rheumatology and Autoimmunity Biochemistry and Molecular Biology Pharmacology and Toxicology
Research subject
cell research; Orthopaedics; Pathology; molecular cell biology
Identifiers
urn:nbn:se:umu:diva-192028 (URN)10.3389/fgene.2021.773534 (DOI)000748023600001 ()35087566 (PubMedID)2-s2.0-85123407841 (Scopus ID)
Available from: 2022-01-31 Created: 2022-01-31 Last updated: 2023-09-05Bibliographically approved
Han, J., Deng, H., Lyu, Y., Xiao, X., Zhao, Y., Liu, J., . . . Lammi, M. (2022). Identification of N-glycoproteins of knee cartilage from adult osteoarthritis and Kashin-Beck disease based on quantitative glycoproteomics, compared with normal control cartilage. Cells, 11(16), 2513-2513, Article ID 36010590.
Open this publication in new window or tab >>Identification of N-glycoproteins of knee cartilage from adult osteoarthritis and Kashin-Beck disease based on quantitative glycoproteomics, compared with normal control cartilage
Show others...
2022 (English)In: Cells, E-ISSN 2073-4409, Vol. 11, no 16, p. 2513-2513, article id 36010590Article in journal (Refereed) Published
Abstract [en]

Glycoproteins are involved in the development of many diseases, while the type and content of N-glycoproteins in the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) are still unclear. This research aims to identify N-glycoproteins in knee cartilage patients with OA and KBD compared with normal control (N) adults. The cartilage samples were collected from gender- and age-matched OA (n = 9), KBD (n = 9) patients, and N (n = 9) adults. Glycoproteomics and label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) obtained N-glycoproteins of KBD and OA. A total of 594 N-glycoproteins and 1146 N-glycosylation peptides were identified. The identified data were further compared and analyzed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interactions (PPI). Pairwise comparison of the glycoproteins detected in the three groups showed that integrin beta-1 (ITGB1), collagen alpha-1 (II) chain (COL2A1), collagen alpha-1 (VII) chain (COL7A1), carbohydrate sulfotransferase 3 (CHST-3), carbohydrate sulfotransferase 4 (CHST-4), thrombospondin 2 (THBS2), bone morphogenetic protein 8A (BMP8A), tenascin-C (TNC), lysosome-associated membrane protein (LAMP2), and beta-glucuronidase (GUSB) were significantly differentially expressed. GO results suggested N-glycoproteins mainly belonged to protein metabolic process, single-multicellular and multicellular organism process, cell adhesion, biological adhesion, and multicellular organism development. KEGG and PPI results revealed that key N-glycoproteins were closely related to pathways for OA and KBD, such as phagosome, ECM-receptor interaction, lysosome, focal adhesion, protein digestion, and absorption. These results reflected glycoprotein expression for OA and KBD in the process of ECM degradation, material transport, cell-cell or cell-ECM interaction, and information transduction. These key significantly differentially expressed N-glycoproteins and pathways lead to the degeneration and degradation of the cartilage of OA and KBD mainly by disrupting the synthesis and catabolism of basic components of ECM and chondrocytes and interfering with the transfer of material or information. The key N-glycoproteins or pathways in this research are potential targets for pathological mechanisms and therapies of OA and KBD.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
Kashin–Beck disease, cartilage, glycoproteins, osteoarthritis
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Rheumatology and Autoimmunity Biochemistry and Molecular Biology
Research subject
Biochemistry; rheumatology; cell research
Identifiers
urn:nbn:se:umu:diva-198957 (URN)10.3390/cells11162513 (DOI)000846119000001 ()36010590 (PubMedID)2-s2.0-85136644042 (Scopus ID)
Available from: 2022-08-29 Created: 2022-08-29 Last updated: 2022-09-09Bibliographically approved
Lyu, Y., Deng, H., Qu, C., Qiao, L., Liu, X., Xiao, X., . . . Lammi, M. (2022). Identification of proteins and N-glycosylation sites of knee cartilage in Kashin-Beck Disease compared with osteoarthritis. International Journal of Biological Macromolecules, 210, 128-138
Open this publication in new window or tab >>Identification of proteins and N-glycosylation sites of knee cartilage in Kashin-Beck Disease compared with osteoarthritis
Show others...
2022 (English)In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 210, p. 128-138Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to identify crucial proteins and N-glycosylated sites in the pathological mechanism of Kashin-Beck Disease (KBD) compared with osteoarthritis (OA). Nine KBD knee subjects and nine OA knee subjects were selected for the study. Quantitative proteomics and N-glycoproteomics data of KBD and OA were obtained by protein and N-glycoprotein enrichment and LC-MS/MS analysis. Differentially expressed proteins or N-glycosylation sites were examined with a comparative analysis between KBD and OA. Total 2205 proteins were identified in proteomic analysis, of which 375 were significantly different. Among these, 121 proteins were up-regulated and 254 were down-regulated. In N-glycoproteomic analysis, 278 different N-glycosylated sites that were related to 187 N-glycoproteins were identified. Proteins and their N-glycosylated sites are associated with KBD pathological process including ITGB1, LRP1, ANO6, COL1A1, MXRA5, DPP4, and CSPG4. CRLF1 and GLG1 are proposed to associate with both KBD and OA pathological processes. Key pathways in KBD vs. OA proteomic and N-glycoproteomic analysis contained extracellular matrix receptor interaction, focal adhesion, phagosome, protein digestion, and absorption. N-glycosylation may influence the pathological process by affecting the integrity of chondrocytes or cartilage. It regulated the intercellular signal transduction pathway, which contributes to cartilage destruction in KBD.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Kashin-Beck disease, N-glycoproteomics, N-glycosylated sites, Osteoarthritis, Proteomics
National Category
Biochemistry and Molecular Biology Cell and Molecular Biology Orthopaedics
Research subject
Biochemistry; rheumatology; Orthopaedics
Identifiers
urn:nbn:se:umu:diva-194606 (URN)10.1016/j.ijbiomac.2022.05.014 (DOI)000806361400005 ()35526762 (PubMedID)2-s2.0-85129751455 (Scopus ID)
Available from: 2022-05-11 Created: 2022-05-11 Last updated: 2023-09-05Bibliographically approved
Liu, H., Wu, C., Zhao, H., Zhang, F., Zhao, G., Lin, X., . . . Guo, X. (2022). The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway. The FEBS Journal, 289(1), 279-293
Open this publication in new window or tab >>The first human induced pluripotent stem cell line of Kashin–Beck disease reveals involvement of heparan sulfate proteoglycan biosynthesis and PPAR pathway
Show others...
2022 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 289, no 1, p. 279-293Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Kashin-Beck disease (KBD) is an endemic osteochondropathy. Due to a lack of suitable animal or cellular disease models, the research progress on KBD has been limited. Our goal was to establish the first disease-specific human induced pluripotent stem cells (hiPSCs) cellular disease model of KBD, and to explore its etiology and pathogenesis exploiting transcriptome sequencing.

METHODS: HiPSCs were reprogrammed from dermal fibroblasts of two KBD and one healthy control donors via integration-free vectors. Subsequently, hiPSCs were differentiated into chondrocytes through three-week culture. Gene expression profiles in KBD, normal primary chondrocytes and hiPSC-derived chondrocytes were defined by RNA sequencing. A Venn diagram was constructed to show the number of shared differentially expressed genes (DEGs) between KBD and normal. Gene oncology and Kyoto Encyclopedia of Genes and Genomes annotations were performed, and six DEGs were further validated in other individuals by real-time quantitative reverse transcription PCR (RT-qPCR).

RESULTS: KBD cellular disease models were successfully established by generation of hiPSC lines. Seventeen consistent and significant DEGs present in all compared groups (KBD and normal) were identified. RT-qPCR validation gave consistent results with the sequencing data. Glycosaminoglycan biosynthesis-heparan sulfate/heparin, PPAR signaling pathway and cell adhesion molecules (CAMs) pathways were identified to be significantly altered in KBD.

CONCLUSION: Differentiated chondrocytes deriving from KBD-origin hiPSCs provide the first cellular disease model for etiological studies of KBD. This study also provides new sights into the pathogenesis and etiology of KBD and is likely to inform the development of targeted therapeutics for its treatment.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
Chondrogenesis, Disease model, Heparan sulfate proteoglycans, Human induced pluripotent stem cells, Kashin-Beck disease
National Category
Orthopaedics Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Rheumatology and Autoimmunity
Research subject
cell research; Orthopaedics; rheumatology
Identifiers
urn:nbn:se:umu:diva-186450 (URN)10.1111/febs.16143 (DOI)000682366500001 ()34324261 (PubMedID)2-s2.0-85112624359 (Scopus ID)
Available from: 2021-08-02 Created: 2021-08-02 Last updated: 2022-01-25Bibliographically approved
Wang, X., Ning, Y., Li, C., Gong, Y., Huang, R., Hu, M., . . . Guo, X. (2021). Alterations in the gut microbiota and metabolite profiles of patients with Kashin-Beck disease, an endemic osteoarthritis in China. Cell Death and Disease, 12(11), Article ID 1015.
Open this publication in new window or tab >>Alterations in the gut microbiota and metabolite profiles of patients with Kashin-Beck disease, an endemic osteoarthritis in China
Show others...
2021 (English)In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 12, no 11, article id 1015Article in journal (Refereed) Published
Abstract [en]

Kashin-Beck disease (KBD) is a severe osteochondral disorder that may be driven by the interaction between genetic and environmental factors. We aimed to improve our understanding of the gut microbiota structure in KBD patients of different grades and the relationship between the gut microbiota and serum metabolites. Fecal and serum samples collected from KBD patients and normal controls (NCs) were used to characterize the gut microbiota using 16S rDNA gene and metabolomic sequencing via liquid chromatography-mass spectrometry (LC/MS). To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria in the KBD patients, metagenomic sequencing of fecal samples from grade I KBD, grade II KBD and NC subjects was performed. The KBD group was characterized by elevated levels of Fusobacteria and Bacteroidetes. A total of 56 genera were identified to be significantly differentially abundant between the two groups. The genera Alloprevotella, Robinsoniella, Megamonas, and Escherichia_Shigella were more abundant in the KBD group. Consistent with the 16S rDNA analysis at the genus level, most of the differentially abundant species in KBD subjects belonged to the genus Prevotella according to metagenomic sequencing. Serum metabolomic analysis identified some differentially abundant metabolites among the grade I and II KBD and NC groups that were involved in lipid metabolism metabolic networks, such as that for unsaturated fatty acids and glycerophospholipids. Furthermore, we found that these differences in metabolite levels were associated with altered abundances of specific species. Our study provides a comprehensive landscape of the gut microbiota and metabolites in KBD patients and provides substantial evidence of a novel interplay between the gut microbiome and metabolome in KBD pathogenesis.

Place, publisher, year, edition, pages
Nature Publishing Group, 2021
Keywords
Gut microbiota, metabolites, Kashin-Beck disease
National Category
Orthopaedics Rheumatology and Autoimmunity Microbiology in the medical area
Research subject
Microbiology; Orthopaedics; rheumatology
Identifiers
urn:nbn:se:umu:diva-189017 (URN)10.1038/s41419-021-04322-2 (DOI)000712529700003 ()34711812 (PubMedID)2-s2.0-85118337287 (Scopus ID)
Available from: 2021-11-01 Created: 2021-11-01 Last updated: 2023-03-23Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6181-9904

Search in DiVA

Show all publications