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Constitutive bone marrow adipocytes suppress local bone formation and support hematopoietic stem and progenitor cells

ABSTRACT: Methods: Whole distal tibial bones were collected from male control or BMAd-DTA mice at 24 weeks of age. Results: Using an optimized data analysis workflow, we mapped over 20 million sequence reads per sample to the mouse genome (UCSC mm10) and identified 22,600 transcripts in the whole distal tibial bones of control or BMAd-DTA mice using STAR with default parameters. We identified 841 genes that were significantly changed in BMAd-DTA mice; of these, 432 genes were up-regulated. Pathway analysis revealed that this gene set is enriched in ossification, extracellular matrix organization, and osteoblast differentiation pathways. Conclusion: The increased bone mass in BMAd-DTA mice appears to be secondary to enhanced bone formation, suggesting a local effect caused by depletion of BMAd.

ORGANISM(S): Mus musculus

PROVIDER: GSE199973 | GEO | 2022/09/01

REPOSITORIES: GEO

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Project description:Objective: Craniofacial bone defects caused by injuries and congenital diseases are a formidable challenge to clinicians. Research has shown promise in using bone marrow mesenchymal stem cells (BM-MSCs) from limb bones for craniofacial bone regeneration; yet little is known about the potential of BM-MSCs from craniofacial bones. This study compared BM-MSCs isolated from limb and craniofacial bones in pigs, a preclinical model closely resembling humans. Design: Bone marrow was aspirated from the tibia and mandible of four-month-old pigs (n=4), followed by BM-MSC isolation, culture-expansion and confirmation by flow cytometry. Proliferation rates were compared using population doubling times. Osteogenic differentiation was evaluated by quantifying alkaline phosphatase (ALP) activity. Total mRNA was extracted from freshly isolated BM-MSCs and analyzed to compare gene expressions of tibial and mandibular BM-MSCs using an Affymetrix GeneChip porcine genome array, followed by real-time RT-PCR evaluation of two neural crest markers. Results: BM-MSCs from both locations expressed MSC markers without expression of hematopoietic markers. Mandibular BM-MSCs proliferated significantly faster than tibial BM-MSCs. Without osteogenic inducers, mandibular BM-MSC alkaline phosphatase activities were 3.3-fold greater than those of tibial origin. Microarray analysis identified 383 differentially expressed genes in mandibular and tibial BM-MSCs, including higher expression of cranial neural crest-related genes nestin and BMP-4 in mandibular BM-MSCs, a trend also confirmed by real-time RT-PCR. Among differently expressed genes, only 47 showed greater than 1.5-fold differences in expression. Conclusions: These data indicate that despite many similarities in gene expression, mandibular BM-MSCs express of number of genes differently than tibial BM-MSCs and have a phenotypic profile that may make them advantageous for craniofacial bone regeneration. Bone marrow was aspirated from the mandibular symphyseal region and the tibia of 3 pigs. Mesenchymal stem cells were isolated from the bone marrow and cultured to 80% confluence. Cells were harvested for total RNA extraction and the RNA was analyzed by Affymetrix GeneChip porcine genome array.

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Constitutive bone marrow adipocytes suppress local bone formation and support hematopoietic stem and progenitor cells

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