Skeleton interoception regulates bone and fat metabolism through hypothalamic neuroendocrine NPY

Lv, Xiao; Gao, Feng; Li, Tuo Peter; Xue, Peng; Wang, Xiao; Wan, Mei; Hu, Bo; Chen, Hao; Jain, Amit; Shao, Zengwu; Cao, Xu

doi:10.7554/elife.70324

Cited by 23 publications

(20 citation statements)

References 63 publications

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“…This gene might have been a novel loci associated with the human skeletal frame size ( 32 ). PTGER4 encodes a protein that is one of the members of the G-protein coupled receptor family, which imparts relaxation to the smooth muscle ( 34 ), leading to the phosphorylation of glycogen synthase kinase-3 ( 35 ), involved in osteoporosis ( 36 ), and regulating lipid droplet size and mitochondrial activity in the white adipose tissue ( 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association analysis of milk production, somatic cell score, and body conformation traits in Holstein cows

et al. 2022

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Milk production and body conformation traits are critical economic traits for dairy cows. To understand the basic genetic structure for those traits, a genome wide association study was performed on milk yield, milk fat yield, milk fat percentage, milk protein yield, milk protein percentage, somatic cell score, body form composite index, daily capacity composite index, feed, and leg conformation traits, based on the Illumina Bovine HD100k BeadChip. A total of 57, 12 and 26 SNPs were found to be related to the milk production, somatic cell score and body conformation traits in the Holstein cattle. Genes with pleiotropic effect were also found in this study. Seven significant SNPs were associated with multi-traits and were located on the PLEC, PLEKHA5, TONSL, PTGER4, and LCORL genes. In addition, some important candidate genes, like GPAT3, CEBPB, AGO2, SLC37A1, and FNDC3B, were found to participate in fat metabolism or mammary gland development. These results can be used as candidate genes for milk production, somatic cell score, and body conformation traits of Holstein cows, and are helpful for further gene function analysis to improve milk production and quality.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association analysis of milk production, somatic cell score, and body conformation traits in Holstein cows

et al. 2022

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“…The major DEG whose products are contributors to bone formation and osteoblast function included transcription factors ( Gli1 , ( 44 ) Satb2 , ( 45 ) Sox8 , ( 46 ) Foxp1 ( 47 ) ), enzymes ( Chka , ( 48 ) Lox , ( 49 ) Cdo1 ( 50 ) ), and matrix‐related genes ( Vcan , ( 51 ) Gorab , ( 52 ) Kdelr2 ( 53 ) ). Osteoblast‐related genes Npy and Axin2 were upregulated with loading and respectively encode a neuropeptide that binds to its receptor on osteoblasts to enhance their function ( 54 ) and a regulator of Wnt signaling, a major osteogenic pathway. ( 55 ) Two osteoclast‐related genes linked to resorption, Fam98a ( 56 ) and Traf6 , ( 57 ) were also upregulated with loading, whereas Ttpa , ( 58 ) a gene whose product attenuates osteoclastogenesis, was downregulated.…”

Section: Resultsmentioning

confidence: 99%

Molecular Identification of Spatially Distinct Anabolic Responses to Mechanical Loading in Murine Cortical Bone

Chlebek

Moore

Ross

et al. 2020

Journal of Bone and Mineral Research

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Osteoporosis affects over 200 million women worldwide, one-third of whom are predicted to suffer from an osteoporotic fracture in their lifetime. The most promising anabolic drugs involve administration of expensive antibodies. Because mechanical loading stimulates bone formation, our current data, using a mouse model, replicates the anabolic effects of loading in humans and may identify novel pathways amenable to oral treatment. Murine tibial compression produces axially varying deformations along the cortical bone, inducing highest strains at the mid-diaphysis and lowest at the metaphyseal shell. To test the hypothesis that load-induced transcriptomic responses at different axial locations of cortical bone would vary as a function of strain magnitude, we loaded the left tibias of 10-week-old female C57Bl/6 mice in vivo in compression, with contralateral limbs as controls. Animals were euthanized at 1, 3, or 24 hours post-loading or loaded for 1 week (n = 4-5/group). Bone marrow and cancellous bone were removed, cortical bone was segmented into the metaphyseal shell, proximal diaphysis, and mid-diaphysis, and load-induced differential gene expression and enriched biological processes were examined for the three segments. At each time point, the mid-diaphysis (highest strain) had the greatest transcriptomic response. Similarly, biological processes regulating bone formation and turnover increased earlier and to the greatest extent at the mid-diaphysis. Higher strain induced greater levels of osteoblast and osteocyte genes, whereas expression was lower in osteoclasts. Among the top differentially expressed genes at 24-hours post-loading, 17 had known functions in bone biology, of which 12 were present only in osteoblasts, 3 exclusively in osteoclasts, and 2 were present in both cell types. Based on these results, we conclude that murine tibial loading induces spatially unique transcriptomic responses correlating with strain magnitude in cortical bone.

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“…The role of NPY in bone metabolism is multifaceted (41). On the one hand, NPY can lead to a decrease in bone mass by combining with Y1 receptors (42,43). On the other hand, NPY exhibits an osteoprotective effect by directly promoting the proliferation and osteogenic differentiation of MSCs (44)(45)(46)(47) and combining Y1 receptors in macrophages to maintain the activity of stem cells (18).…”

Section: Discussionmentioning

confidence: 99%

The interplay between the nerves and skeleton: a 30-year bibliometric analysis

Mei¹,

Wu²,

Feng³

et al. 2023

Ann Transl Med

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Background The mechanisms and effects of the interplay between the nerves and skeleton remain a popular research topic. This study aimed to analyze and evaluate publications on nerve-bone interactions using bibliometrics and to identify the state of the art of current research, hotspots, and future directions. Methods This study included 1989 articles and reviews from the Web of Science Core Collection (WoSCC) published from January 1, 1991, to June 22, 2022. The Bibliometrix package of R 4.2.0 (The R Foundation for Statistical Computing, Vienna, Austria) was used to analyze basic information about the publications, including the annual number of publications, institution analysis, author influence analysis, journal analysis, and the national cooperation network. We also used CiteSpace 5.8.R3 for bibliometric analysis, including co-occurrence, co-citation, and cluster analysis. Results We discovered a significant increase in the number of articles on nerve-bone interactions published over the last 10 years. The most active country and institution were the United States and the University of Minnesota, respectively. In terms of journals and cocited journals, Bone was ranked highest with respect to the number of publications, while Journal of Bone and Mineral Research was ranked highest among cited journals. Wang Lei was the author with the most publications, and Bjurholm A was the most cited author. The analysis of references and keywords revealed that the impact of nerve- and neuromodulation-related factors on stem cell differentiation was a persistently hot topic. Osteoarthritis, neuropeptide Y, and osteoclastogenic process are likely to be the next era of research hotspots. The neurovascular crosstalk within bone has received great attention, especially in skeletal diseases, which may provide potential targets for future treatments. Conclusions We used a bibliometric method to provide an efficient, objective, and comprehensive assessment of existing research about the interplay between the skeletal and nervous systems and to accurately identify hotspots and research frontiers, providing valuable information for future research.

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Skeleton interoception regulates bone and fat metabolism through hypothalamic neuroendocrine NPY

Cited by 23 publications

References 63 publications

Genome-wide association analysis of milk production, somatic cell score, and body conformation traits in Holstein cows

Genome-wide association analysis of milk production, somatic cell score, and body conformation traits in Holstein cows

Molecular Identification of Spatially Distinct Anabolic Responses to Mechanical Loading in Murine Cortical Bone

The interplay between the nerves and skeleton: a 30-year bibliometric analysis

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