Top

Calcified Tissue International

Published in:

01-08-2019 | Osteoporosis | Original Research

Long Noncoding RNA Analyses for Osteoporosis Risk in Caucasian Women

Authors: Yu Zhou, Chao Xu, Wei Zhu, Hao He, Lan Zhang, Beisha Tang, Yong Zeng, Qing Tian, Hong-Wen Deng

Published in: Calcified Tissue International | Issue 2/2019

Abstract

Introduction

Osteoporosis is a prevalent bone metabolic disease characterized by bone fragility. As a key pathophysiological mechanism, the disease is caused by excessive bone resorption (by osteoclasts) over bone formation (by osteoblasts). Peripheral blood monocytes (PBMs) is a major systemic cell model for bone metabolism by serving as progenitors of osteoclasts and producing cytokines important for osteoclastogenesis. Protein-coding genes for osteoporosis have been widely studied by mRNA analyses of PBMs in high versus low hip bone mineral density (BMD) subjects. However, long noncoding RNAs (lncRNAs), which account for a large proportion of human transcriptome, have seldom been studied.

Methods

In this study, microarray analyses of monocytes were performed using Affymetrix exon 1.0 ST arrays in 73 Caucasian females (age: 47–56). LncRNA profile was generated by re-annotating exon array for lncRNAs detection, which yielded 12,007 lncRNAs mapped to the human genome.

Results

575 lncRNAs were differentially expressed between the two groups. In the high BMD subjects, 309 lncRNAs were upregulated and 266 lncRNAs were downregulated (nominally significant, raw p-value < 0.05). To investigate the relationship between mRNAs and lncRNAs, we used two approaches to predict the target genes of lncRNAs and found that 26 candidate lncRNAs might regulate mRNA expression. The majority of these lncRNAs were further validated to be potentially correlated with BMD by GWAS analysis.

Conclusion

Overall, our findings for the first time reported the lncRNAs profiles for osteoporosis and suggested the potential regulatory mechanism of lncRNAs on protein-coding genes in bone metabolism.

Zhou Y, Deng HW, Shen H (2015) Circulating monocytes: an appropriate model for bone-related study. Osteoporos Int 26(11):2561–2572. https://doi.org/10.1007/s00198-015-3250-7 View ArticlePubMed
Fujikawa Y, Quinn JM, Sabokbar A, McGee JO, Athanasou NA (1996) The human osteoclast precursor circulates in the monocyte fraction. Endocrinology 137(9):4058–4060. https://doi.org/10.1210/endo.137.9.8756585 View ArticlePubMed
Higuchi S, Tabata N, Tajima M, Ito M, Tsurudome M, Sudo A, Uchida A, Ito Y (1998) Induction of human osteoclast-like cells by treatment of blood monocytes with anti-fusion regulatory protein-1/CD98 monoclonal antibodies. J Bone Miner Res 13(1):44–49. https://doi.org/10.1359/jbmr.1998.13.1.44 View ArticlePubMed
Matayoshi A, Brown C, DiPersio JF, Haug J, Abu-Amer Y, Liapis H, Kuestner R, Pacifici R (1996) Human blood-mobilized hematopoietic precursors differentiate into osteoclasts in the absence of stromal cells. Proc Natl Acad Sci USA 93(20):10785–10790View ArticlePubMedPubMed Central
Purton LE, Lee MY, Torok-Storb B (1996) Normal human peripheral blood mononuclear cells mobilized with granulocyte colony-stimulating factor have increased osteoclastogenic potential compared to nonmobilized blood. Blood 87(5):1802–1808PubMed
Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, Leenen PJ, Liu YJ, MacPherson G, Randolph GJ, Scherberich J, Schmitz J, Shortman K, Sozzani S, Strobl H, Zembala M, Austyn JM, Lutz MB (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116(16):e74–e80. https://doi.org/10.1182/blood-2010-02-258558 View ArticlePubMed
Ziegler-Heitbrock L, Hofer TP (2013) Toward a refined definition of monocyte subsets. Front Immunol 4:23. https://doi.org/10.3389/fimmu.2013.00023 View ArticlePubMedPubMed Central
Komano Y, Nanki T, Hayashida K, Taniguchi K, Miyasaka N (2006) Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts. Arthritis Res Ther 8(5):R152. https://doi.org/10.1186/ar2046 View ArticlePubMedPubMed Central
Custer RPAF (1932) Studies of the structure and function of bone marrow: variations in cellularity in various bones with advancing years of life and their relative response to stimuli. J Lab Clin Med 17:960–962
Horton MA, Spragg JH, Bodary SC, Helfrich MH (1994) Recognition of cryptic sites in human and mouse laminins by rat osteoclasts is mediated by beta 3 and beta 1 integrins. Bone 15(6):639–646View ArticlePubMed
Parfitt AM (1994) Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 55(3):273–286. https://doi.org/10.1002/jcb.240550303 View ArticlePubMed
Parfitt AM (1998) Osteoclast precursors as leukocytes: importance of the area code. Bone 23(6):491–494View ArticlePubMed
Zallone AZ, Teti A, Primavera MV (1984) Monocytes from circulating blood fuse in vitro with purified osteoclasts in primary culture. J Cell Sci 66:335–342
Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166. https://doi.org/10.1146/annurev-biochem-051410-092902 View ArticlePubMed
Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152(6):1298–1307. https://doi.org/10.1016/j.cell.2013.02.012 View ArticlePubMedPubMed Central
Tavares L, Dimitrova E, Oxley D, Webster J, Poot R, Demmers J, Bezstarosti K, Taylor S, Ura H, Koide H, Wutz A, Vidal M, Elderkin S, Brockdorff N (2012) RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3. Cell 148(4):664–678. https://doi.org/10.1016/j.cell.2011.12.029 View ArticlePubMedPubMed Central
Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, Nagano T, Mancini-Dinardo D, Kanduri C (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32(2):232–246. https://doi.org/10.1016/j.molcel.2008.08.022 View ArticlePubMed
Chu C, Qu K, Zhong FL, Artandi SE, Chang HY (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell 44(4):667–678. https://doi.org/10.1016/j.molcel.2011.08.027 View ArticlePubMedPubMed Central
Tong X, Gu PC, Xu SZ, Lin XJ (2015) Long non-coding RNA-DANCR in human circulating monocytes: a potential biomarker associated with postmenopausal osteoporosis. Biosci Biotechnol Biochem 79(5):732–737. https://doi.org/10.1080/09168451.2014.998617 View ArticlePubMed
Dou C, Cao Z, Yang B, Ding N, Hou T, Luo F, Kang F, Li J, Yang X, Jiang H, Xiang J, Quan H, Xu J, Dong S (2016) Changing expression profiles of lncRNAs, mRNAs, circRNAs and miRNAs during osteoclastogenesis. Sci Rep 6:21499. https://doi.org/10.1038/srep21499 View ArticlePubMedPubMed Central
Michelhaugh SK, Lipovich L, Blythe J, Jia H, Kapatos G, Bannon MJ (2011) Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers. J Neurochem 116(3):459–466. https://doi.org/10.1111/j.1471-4159.2010.07126.x View ArticlePubMed
Johnson R (2012) Long non-coding RNAs in Huntington’s disease neurodegeneration. Neurobiol Dis 46(2):245–254. https://doi.org/10.1016/j.nbd.2011.12.006 View ArticlePubMed
Dinger ME, Pang KC, Mercer TR, Crowe ML, Grimmond SM, Mattick JS (2009) NRED: a database of long noncoding RNA expression. Nucleic Acids Res 37(Database issue):D122–D126. https://doi.org/10.1093/nar/gkn617 View ArticlePubMed
Gellert P, Ponomareva Y, Braun T, Uchida S (2013) Noncoder: a web interface for exon array-based detection of long non-coding RNAs. Nucleic Acids Res 41(1):e20. https://doi.org/10.1093/nar/gks877 View ArticlePubMed
Du Z, Fei T, Verhaak RG, Su Z, Zhang Y, Brown M, Chen Y, Liu XS (2013) Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat Struct Mol Biol 20(7):908–913. https://doi.org/10.1038/nsmb.2591 View ArticlePubMedPubMed Central
Liu YZ, Zhou Y, Zhang L, Li J, Tian Q, Zhang JG, Deng HW (2015) Attenuated monocyte apoptosis, a new mechanism for osteoporosis suggested by a transcriptome-wide expression study of monocytes. PLoS ONE 10(2):e0116792. https://doi.org/10.1371/journal.pone.0116792 View ArticlePubMedPubMed Central
Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315. https://doi.org/10.1093/bioinformatics/btg405 View ArticlePubMed
Kendziorski C, Irizarry RA, Chen KS, Haag JD, Gould MN (2005) On the utility of pooling biological samples in microarray experiments. Proc Natl Acad Sci USA 102(12):4252–4257. https://doi.org/10.1073/pnas.0500607102 View ArticlePubMedPubMed Central
Smyth GK (2005) Limma: linear models for microarray data. Bioinformatics and computational biology solutions using R and bioconductor. Springer, New York, pp 397–420View Article
Lee M-LT (2004) Analysis of microarray gene expression data. Kluwer Academic Publishers, Boston
Lee ML, Whitmore GA (2002) Power and sample size for DNA microarray studies. Stat Med 21(23):3543–3570. https://doi.org/10.1002/sim.1335 View ArticlePubMed
Ponjavic J, Ponting CP, Lunter G (2007) Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Res 17(5):556–565. https://doi.org/10.1101/gr.6036807 View ArticlePubMedPubMed Central
Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136(4):629–641. https://doi.org/10.1016/j.cell.2009.02.006 View ArticlePubMed
Guenzl PM, Barlow DP (2012) Macro lncRNAs: a new layer of cis-regulatory information in the mammalian genome. RNA Biol 9(6):731–741. https://doi.org/10.4161/rna.19985 View ArticlePubMed
Wang M, Liu W, Jiao J, Li J, Wang C, Zhang L (2017) Expression profiling of mRNAs and long non-coding RNAs in aged mouse olfactory bulb. Sci Rep 7(1):2079. https://doi.org/10.1038/s41598-017-02329-4 View ArticlePubMedPubMed Central
Fan H, Zhang Q, Zhao X, Lv P, Liu M, Tang H (2017) Transcriptomic profiling of long non-coding RNAs in hepatitis B virus-related hepatocellular carcinoma. Oncotarget 8(39):65421–65434. https://doi.org/10.18632/oncotarget.18897 View ArticlePubMedPubMed Central
Zhang J, Feng C, Song C, Ai B, Bai X, Liu Y, Li X, Zhao J, Shi S, Chen X, Su X, Li C (2018) Identification and analysis of a key long non-coding RNAs (lncRNAs)-associated module reveal functional lncRNAs in cardiac hypertrophy. J Cell Mol Med 22(2):892–903. https://doi.org/10.1111/jcmm.13376 View ArticlePubMed
Gao J, Tarcea VG, Karnovsky A, Mirel BR, Weymouth TE, Beecher CW, Cavalcoli JD, Athey BD, Omenn GS, Burant CF, Jagadish HV (2010) Metscape: a Cytoscape plug-in for visualizing and interpreting metabolomic data in the context of human metabolic networks. Bioinformatics 26(7):971–973. https://doi.org/10.1093/bioinformatics/btq048 View ArticlePubMedPubMed Central
Zheng HF, Forgetta V, Hsu YH, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu CT, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, McCarthy S, Eriksson J, Kwan T, Jhamai M, Trajanoska K, Memari Y, Min J, Huang J, Danecek P, Wilmot B, Li R, Chou WC, Mokry LE, Moayyeri A, Claussnitzer M, Cheng CH, Cheung W, Medina-Gomez C, Ge B, Chen SH, Choi K, Oei L, Fraser J, Kraaij R, Hibbs MA, Gregson CL, Paquette D, Hofman A, Wibom C, Tranah GJ, Marshall M, Gardiner BB, Cremin K, Auer P, Hsu L, Ring S, Tung JY, Thorleifsson G, Enneman AW, van Schoor NM, de Groot LC, van der Velde N, Melin B, Kemp JP, Christiansen C, Sayers A, Zhou Y, Calderari S, van Rooij J, Carlson C, Peters U, Berlivet S, Dostie J, Uitterlinden AG, Williams SR, Farber C, Grinberg D, LaCroix AZ, Haessler J, Chasman DI, Giulianini F, Rose LM, Ridker PM, Eisman JA, Nguyen TV, Center JR, Nogues X, Garcia-Giralt N, Launer LL, Gudnason V, Mellstrom D, Vandenput L, Amin N, van Duijn CM, Karlsson MK, Ljunggren O, Svensson O, Hallmans G, Rousseau F, Giroux S, Bussiere J, Arp PP, Koromani F, Prince RL, Lewis JR, Langdahl BL, Hermann AP, Jensen JE, Kaptoge S, Khaw KT, Reeve J, Formosa MM, Xuereb-Anastasi A, Akesson K, McGuigan FE, Garg G, Olmos JM, Zarrabeitia MT, Riancho JA, Ralston SH, Alonso N, Jiang X, Goltzman D, Pastinen T, Grundberg E, Gauguier D, Orwoll ES, Karasik D, Davey-Smith G, Consortium A, Smith AV, Siggeirsdottir K, Harris TB, Zillikens MC, van Meurs JB, Thorsteinsdottir U, Maurano MT, Timpson NJ, Soranzo N, Durbin R, Wilson SG, Ntzani EE, Brown MA, Stefansson K, Hinds DA, Spector T, Cupples LA, Ohlsson C, Greenwood CM, Consortium UK, Jackson RD, Rowe DW, Loomis CA, Evans DM, Ackert-Bicknell CL, Joyner AL, Duncan EL, Kiel DP, Rivadeneira F, Richards JB (2015) Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 526(7571):112–117. https://doi.org/10.1038/nature14878 View ArticlePubMedPubMed Central
Friedman J, Hastie T, Tibshirani R (2010) Regularization paths for generalized linear models via coordinate descent. J Stat Softw 33(1):1–22View ArticlePubMedPubMed Central
Tibshirani R, Bien J, Friedman J, Hastie T, Simon N, Taylor J, Tibshirani RJ (2012) Strong rules for discarding predictors in lasso-type problems. J R Stat Soc Ser B Stat Methodol 74(2):245–266. https://doi.org/10.1111/j.1467-9868.2011.01004.x View Article
Liu Q, Zhang X, Dai L, Hu X, Zhu J, Li L, Zhou C, Ao Y (2014) Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis. Arthritis Rheumatol 66(4):969–978. https://doi.org/10.1002/art.38309 View ArticlePubMed
Li JP, Liu LH, Li J, Chen Y, Jiang XW, Ouyang YR, Liu YQ, Zhong H, Li H, Xiao T (2013) Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun 433(2):200–206. https://doi.org/10.1016/j.bbrc.2013.02.083 View ArticlePubMed
Wang L, Li Z, Li Z, Yu B, Wang Y (2015) Long noncoding RNAs expression signatures in chondrogenic differentiation of human bone marrow mesenchymal stem cells. Biochem Biophys Res Commun 456(1):459–464. https://doi.org/10.1016/j.bbrc.2014.11.106 View ArticlePubMed
Zuo C, Wang Z, Lu H, Dai Z, Liu X, Cui L (2013) Expression profiling of lncRNAs in C3H10T1/2 mesenchymal stem cells undergoing early osteoblast differentiation. Mol Med Rep 8(2):463–467. https://doi.org/10.3892/mmr.2013.1540 View ArticlePubMed
Li X, Wei W, Huynh H, Zuo H, Wang X, Wan Y (2015) Nur77 prevents excessive osteoclastogenesis by inducing ubiquitin ligase Cbl-b to mediate NFATc1 self-limitation. Elife 4:e07217. https://doi.org/10.7554/eLife.07217 View ArticlePubMedPubMed Central
Irie A, Yamamoto K, Miki Y, Murakami M (2017) Phosphatidylethanolamine dynamics are required for osteoclast fusion. Sci Rep 7:46715. https://doi.org/10.1038/srep46715 View ArticlePubMedPubMed Central
Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Röder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See L-H, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan Y, Wold B, Carninci P, Guigó R, Gingeras TR (2012) Landscape of transcription in human cells. Nature 489:101. https://doi.org/10.1038/nature11233 View ArticlePubMedPubMed Central
Long Y, Wang X, Youmans DT, Cech TR (2017) How do lncRNAs regulate transcription? Sci Adv 3(9):eaao2110. https://doi.org/10.1126/sciadv.aao2110 View ArticlePubMedPubMed Central
Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, Fraser P (2008) The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322(5908):1717. https://doi.org/10.1126/science.1163802 View ArticlePubMed
Bond AM, VanGompel MJW, Sametsky EA, Clark MF, Savage JC, Disterhoft JF, Kohtz JD (2009) Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. Nat Neurosci 12:1020. https://doi.org/10.1038/nn.2371 View ArticlePubMedPubMed Central
Maruyama K, Uematsu S, Kondo T, Takeuchi O, Martino MM, Kawasaki T, Akira S (2013) Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP. J Exp Med 210(10):1947–1960. https://doi.org/10.1084/jem.20130512 View ArticlePubMedPubMed Central
Atkins GJ, Kostakis P, Vincent C, Farrugia AN, Houchins JP, Findlay DM, Evdokiou A, Zannettino AC (2006) RANK expression as a cell surface marker of human osteoclast precursors in peripheral blood, bone marrow, and giant cell tumors of bone. J Bone Miner Res 21(9):1339–1349. https://doi.org/10.1359/jbmr.060604 View ArticlePubMed

Title: Long Noncoding RNA Analyses for Osteoporosis Risk in Caucasian Women
Authors: Yu Zhou
Chao Xu
Wei Zhu
Hao He
Lan Zhang
Beisha Tang
Yong Zeng
Qing Tian
Hong-Wen Deng
Publication date: 01-08-2019
Publisher: Springer US
Keywords: Osteoporosis
Osteoporosis
Published in: Calcified Tissue International / Issue 2/2019
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-019-00555-8

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Long Noncoding RNA Analyses for Osteoporosis Risk in Caucasian Women

Abstract

Introduction

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2019

Identification of Patients with Osteoporotic Vertebral Fractures via Simple Text Search of Routine Radiology Reports

The Association of Aromatic Amino Acids with Incident Hip Fracture, aBMD, and Body Composition from the Cardiovascular Health Study

The Response of Osteoblasts and Bone to Sinusoidal Electromagnetic Fields: Insights from the Literature

Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review

Correction to: Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review

Pharmacological Inhibition of NFκB Reduces Prostate Cancer Related Osteoclastogenesis In Vitro and Osteolysis Ex Vivo

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page