Dataset Information

Human Sex Matters: Y-Linked Lysine Demethylase 5D Drives Accelerated Male Craniofacial Osteogenic Differentiation.

ABSTRACT: Female sex is increasingly associated with a loss of bone mass during aging and an increased risk of developing nonunion fractures. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation in human adult neural crest-derived stem cells (NCSCs). Next to an elevated expression of pro-osteogenic regulators, global transcriptomics revealed Lysine Demethylase 5D (KDM5D) to be highly upregulated in differentiating male NCSCs. Loss of function by siRNA or pharmacological inhibition of KDM5D significantly reduced the osteogenic differentiation capacity of male NCSCs. In summary, we demonstrated craniofacial osteogenic differentiation to be sexually dimorphic with the expression of KDM5D as a prerequisite for accelerated male osteogenic differentiation, emphasizing the analysis of sex-specific differences as a crucial parameter for treating bone defects.

SUBMITTER: Merten M

PROVIDER: S-EPMC8909072 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Human Sex Matters: Y-Linked Lysine Demethylase 5D Drives Accelerated Male Craniofacial Osteogenic Differentiation.

Merten Madlen M Greiner Johannes F W JFW Niemann Tarek T Grosse Venhaus Meike M Kronenberg Daniel D Stange Richard R Wähnert Dirk D Kaltschmidt Christian C Vordemvenne Thomas T Kaltschmidt Barbara B

Cells 20220226 5

Female sex is increasingly associated with a loss of bone mass during aging and an increased risk of developing nonunion fractures. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation in human adult neural crest-derived stem cells (NCSCs). Nex ...[more]

PMID: 35269444

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Project description:The objective of Human Y Chromosome Proteome Project is to map and annotate all proteins encoded by genes on the MSY sequences. Lysine (K)-specific demethylase 5D (KDM5D) is located on the AZFb region of Y chromosome and encode for a JmjC-domain-containing protein. Changes in KDM5D transcript level in prostate cancer have shown in various studies. To investigation the function of KDM5D in prostate cancer, we knocked down the expression of KDM5D in human prostate cancer cell (DU-145) using siRNA approach. Down-regulation of KDM5D was confirmed by qRT-PCR and western-blot analyses. Cell cycle analysis and MTS assay revealed that down-regulation of KDM5D induces cell proliferation. Furthermore, we observed that KDM5D down-regulation could effectively decrease apoptosis, as measured by the propidium iodide flow cytometric assay. To further our study, we investigated the dynamic of KDM5D protein network using shotgun label free quantitative proteomics approach in knockdown and control cell line. In summary, 102 down-regulated and 107 up-regulated proteins were detected from 894 total proteins. Up-regulated proteins mainly activated ribosome biogenesis whereas down-regulated genes were mainly involved in proteolysis, cell death and metabolic process. The result raw files were converted to mzXML format and processed through the global proteome machine (GPM) software (version 2.1.1) of the X!Tandem algorithm (freely available at http://www.thegpm.org). The 16 gel fractions were processed serially for each experiment and the output files were generated as non-redundant, merged files with protein identifications with log (e) values less than -1, for each individual gel fraction. A protein database compiled from NCBI (Homo sapien) was used in GPM to search the tandem mass spectra; the database also included common trypsin and human peptide contaminants. False discovery rates (FDR) were evaluated by searching against a reversed sequence database. Search parameters included MS and MS/MS tolerances of +2 Da and +0.2 Da, carbamidomethylation of cysteine as fixed modifications, oxidation of methionine as variable modifications and tolerance of two missed tryptic cleavages and K/R-P cleavages.

Dataset Information

Human Sex Matters: Y-Linked Lysine Demethylase 5D Drives Accelerated Male Craniofacial Osteogenic Differentiation.

Publications

Human Sex Matters: Y-Linked Lysine Demethylase 5D Drives Accelerated Male Craniofacial Osteogenic Differentiation.

Similar Datasets

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