Transcriptional profiling of fracture-associated cytokines and growth factors identifies transcriptional regulation of osteogenic genes by recombinant-human IL1β

IF 1 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2024-07-21 DOI:10.1016/j.genrep.2024.101989

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Abstract

Signaling molecules secreted during bone fracture healing stimulate molecular and cellular changes to promote healing and tissue regeneration. Molecular characterization of cytokines and growth factors can provide insight into their function and potential application as biologics or drug targets for bone tissue regeneration. Previous studies have identified the expression of IL1B, IL6, IL34, IGF1, ANGPT1, and TGFB3 during osteogenic differentiation and facture healing. In this study, we evaluated the transcriptome of adipose-derived mesenchymal stromal cells (AMSCs) following stimulation with these biological factors and examined their role in osteogenic differentiation. Stimulation of AMSCs with recombinant human (rh)-IL1B led to the largest gene expression changes compared to the other signaling factors including 1411 induced and 541 repressed genes (>2-fold). Rh-IL1B regulated genes included inflammatory (IL1B, IL6, CCL2) and osteogenic (BMP2, RUNX2, TWIST2) genes. Rh-IL1B also induced the expression of BMP2 in bone marrow-derived mesenchymal stromal cells (BMSCs) and bone digest cells. Although no changes in osteogenic differentiation of AMSCs was observed, low concentrations of rh-IL1B (0.1 ng/mL) promoted alkaline phosphatase activity of differentiated bone digest cells. Further, rh-IL1B significantly induced the secretion of BMP2 from these cells. Together this data provides insight into the molecular function of fracture-associated biological factors.

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骨折相关细胞因子和生长因子的转录谱分析确定了重组人 IL1β 对成骨基因的转录调控作用

骨折愈合过程中分泌的信号分子会刺激分子和细胞发生变化，从而促进愈合和组织再生。细胞因子和生长因子的分子特征描述可使人们深入了解它们的功能以及作为生物制剂或药物靶点用于骨组织再生的潜力。先前的研究已经确定了成骨分化和骨折愈合过程中 IL1B、IL6、IL34、IGF1、ANGPT1 和 TGFB3 的表达。在本研究中，我们评估了脂肪间充质基质细胞（AMSCs）在受到这些生物因子刺激后的转录组，并研究了它们在成骨分化中的作用。与其他信号因子相比，重组人（rh）-IL1B 刺激 AMSCs 可导致最大的基因表达变化，包括 1411 个诱导基因和 541 个抑制基因（>2 倍）。Rh-IL1B调控的基因包括炎症基因（IL1B、IL6、CCL2）和成骨基因（BMP2、RUNX2、TWIST2）。Rh-IL1B 还能诱导骨髓间充质基质细胞（BMSCs）和骨消化细胞中 BMP2 的表达。虽然没有观察到 AMSCs 的成骨分化发生变化，但低浓度 rh-IL1B （0.1 ng/mL）可促进分化的骨消化细胞的碱性磷酸酶活性。此外，rh-IL1B 还能显著诱导这些细胞分泌 BMP2。这些数据有助于深入了解骨折相关生物因子的分子功能。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.