RNA-seq in Skeletal Biology

Ayturk, Ugur M.

doi:10.1007/s11914-019-00517-x

Cited by 32 publications

(28 citation statements)

References 77 publications

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“…This is similar to the response seen after anabolic mechanical loading ( Morse et al, 2018 ; Govey et al, 2015 ; Galea et al, 2017 ). This was one of the first studies to use RNAseq to examine changes in gene expression in bone in response to unloading and to compare gene expression across multiple mouse strains ( Ayturk, 2019 ). There were some limitations as we were only able to analyze seven of the mouse strains, and gene expression was analyzed in the tibia while all other measurements were done in the femur.…”

Section: Discussionmentioning

confidence: 99%

Genetic variability affects the skeletal response to immobilization in founder strains of the diversity outbred mouse population

et al. 2021

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Mechanical unloading decreases bone volume and strength. In humans and mice, bone mineral density is highly heritable, and in mice the response to changes in loading varies with genetic background. Thus, genetic variability may affect the response of bone to unloading. As a first step to identify genes involved in bones' response to unloading, we evaluated the effects of unloading in eight inbred mouse strains: C57BL/6J, PWK/PhJ, WSB/EiJ, A/J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, and CAST/EiJ. C57BL/6J and NOD/ShiLtJ mice had the greatest unloading-induced loss of diaphyseal cortical bone volume and strength. NZO/HlLtJ mice had the greatest metaphyseal trabecular bone loss, and C57BL/6J, WSB/EiJ, NOD/ShiLtJ, and CAST/EiJ mice had the greatest epiphyseal trabecular bone loss. Bone loss in the epiphyses displayed the highest heritability. With immobilization, mineral:matrix was reduced, and carbonate:phosphate and crystallinity were increased. A/J mice displayed the greatest unloading-induced loss of mineral:matrix. Changes in gene expression in response to unloading were greatest in NOD/ShiLtJ and CAST/EiJ mice. The most upregulated genes in response to unloading were associated with increased collagen synthesis and extracellular matrix formation. Our results demonstrate a strong differential response to unloading as a function of strain. Diversity outbred (DO) mice are a high-resolution mapping population derived from these eight inbred founder strains. These results suggest DO mice will be highly suited for examining the genetic basis of the skeletal response to unloading.

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Section: Discussionmentioning

confidence: 99%

Genetic variability affects the skeletal response to immobilization in founder strains of the diversity outbred mouse population

et al. 2021

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“…RNA-seq has been applied to drug screening and biomarker detection of drugs because of its high throughput, rapid detection speed, and simple analysis methods [ 10 ]. In addition, RNA-seq has also been widely used in bone biology research to address problems of bone development and bone diseases [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Aqueous Extract of Eucommia Leaves Promotes Proliferation, Differentiation, and Mineralization of Osteoblast-Like MC3T3-E1 Cells

Guan

Pan

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Eucommia leaves are dry leaves of Eucommia ulmoides which have long been considered as a functional health food for the treatment of hypertension, hypercholesterolemia, fatty liver, and osteoporosis. With the recent development of Chinese medicine, Eucommia leaves are widely used for tonifying the kidneys and strengthening bone. However, the specific molecular mechanism of Eucommia leaves for strengthening bone remains largely unknown. Osteoblasts are the main functional cells of bone formation; thus, it is essential to study the effect of Eucommia leaves on osteoblasts to better understand their mechanism of action. In the present study, we prepared an aqueous extract of Eucommia leaves (ELAE) and determined its content by high-performance liquid chromatography (HPLC). The effects of ELAE on MC3T3-E1 cells were investigated by CCK-8 assay, alkaline phosphatase (ALP), and Alizarin red S staining assays, combined with RNA sequencing (RNA-seq) and qRT-PCR validation. We demonstrated that ELAE had a significant promoting effect on the proliferation of MC3T3-E1 cells and significantly enhanced extracellular matrix synthesis and mineralization, which were achieved by regulating various functional genes and related signaling pathways. ELAE significantly increased the expression level of genes promoting cell proliferation, such as Rpl10a, Adnp, Pex1, Inpp4a, Frat2, and Pcdhga1, and reduced the expression level of genes inhibiting cell proliferation, such as Npm1, Eif3e, Cbx3, Psmc6, Fgf7, Fxr1, Ddx3x, Mbnl1, and Cdc27. In addition, ELAE increased the expression level of gene markers in osteoblasts, such as Col5a2, Ubap2l, Dkk3, Foxm1, Col16a1, Col12a1, Usp7, Col4a6, Runx2, Sox4, and Bmp4. Taken together, our results suggest that ELAE could promote osteoblast proliferation, differentiation, and mineralization and prevent osteoblast apoptosis. These findings not only increase our understanding of ELAE on the regulation of bone development but also provide a possible strategy to further study the prevention and treatment of osteogenic related diseases by ELAE.

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“…39,40 This was one of the first studies to use RNAseq to examine changes in gene expression in bone in response to unloading and to compare gene expression across multiple mouse strains. 41 There were some limitations as we were only able to analyze seven of the mouse strains, and gene expression was analyzed in the tibia while all other measurements were done in the femur. Further studies need to be performed to better understand the time course of changes in gene activation with changes in mechanical loading and how genetic variation affects these responses.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variability affects the Skeletal Response to Unloading

Abood

Senwar

et al. 2020

Preprint

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Mechanical unloading decreases bone volume and strength. In humans and mice, bone mineral density is highly heritable, and in mice the response to changes in loading varies with genetic background. Thus, genetic variability may affect the response of bone to unloading. As a first step to identify genes involved in bone response to unloading, we evaluated the effects of unloading in eight inbred mouse strains: C57BL/6J, PWK/PhJ, WSB/EiJ, A/J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, and CAST/EiJ. C57BL/6J and NOD/ShiLtJ mice had the greatest unloading induced loss of diaphyseal cortical bone volume and strength. NZO/HlLtJ mice had the greatest metaphyseal trabecular bone loss, and C57BL/6J, WSB/EiJ, NOD/ShiLtJ, and CAST/EiJ mice had the greatest epiphyseal trabecular loss. Bone loss in the epiphyses displayed the highest heritability. With immobilization, mineral:matrix was reduced, and carbonate:phosphate and crystallinity were increased. A/J mice displayed the greatest unloading induced loss of mineral:matrix. Changes in gene expression in response to unloading were greatest in NOD/ShiLtJ and CAST/EiJ mice. The most upregulated genes in response to unloading were associated with increased collagen synthesis and extracellular matrix formation. Our results demonstrate a strong differential response to unloading as a function of strain. Diversity outbred (DO) mice are a high-resolution mapping population derived from these eight inbred founder strains. These results suggest DO mice will be highly suited for examining the genetic basis of the skeletal response to unloading.

show abstract

RNA-seq in Skeletal Biology

Cited by 32 publications

References 77 publications

Genetic variability affects the skeletal response to immobilization in founder strains of the diversity outbred mouse population

Genetic variability affects the skeletal response to immobilization in founder strains of the diversity outbred mouse population

The Aqueous Extract of Eucommia Leaves Promotes Proliferation, Differentiation, and Mineralization of Osteoblast-Like MC3T3-E1 Cells

Genetic Variability affects the Skeletal Response to Unloading

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