The Expression and Function of Metastases Associated Lung Adenocarcinoma Transcript-1 Long Non-Coding RNA in Subchondral Bone and Osteoblasts from Patients with Osteoarthritis

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Apr 30

PMID 33916321

Citations 5

Authors

Fawzeyah A Alnajjar

Archana Sharma-Oates

Susanne N Wijesinghe

Hussein Farah

Dominika E Nanus

Tom Nicholson

Edward T Davis

Simon W Jones

Affiliations

Soon will be listed here.

Abstract

Metastasis Associated Lung Adenocarcinoma Transcript-1 (MALAT1) is implicated in regulating the inflammatory response and in the pathology of several chronic inflammatory diseases, including osteoarthritis (OA). The purpose of this study was to examine the relationship between OA subchondral bone expression of MALAT1 with parameters of joint health and biomarkers of joint inflammation, and to determine its functional role in human OA osteoblasts. Subchondral bone and blood were collected from hip and knee OA patients ( = 17) and bone only from neck of femur fracture patients ( = 6) undergoing joint replacement surgery. Cytokines were determined by multiplex assays and ELISA, and gene expression by qPCR. MALAT1 loss of function was performed in OA patient osteoblasts using locked nucleic acids. The osteoblast transcriptome was analysed by RNASeq and pathway analysis. Bone expression of MALAT1 positively correlated to serum DKK1 and galectin-1 concentrations, and in OA patient osteoblasts was induced in response to IL-1β stimulation. Osteoblasts depleted of MALAT1 exhibited differential expression (>1.5 fold change) of 155 genes, including PTGS2. Both basal and IL-1β-mediated PGE2 secretion was greater in MALAT1 depleted osteoblasts. The induction of MALAT1 in human OA osteoblasts upon inflammatory challenge and its modulation of PGE2 production suggests that MALAT1 may play a role in regulating inflammation in OA subchondral bone.

Citing Articles

The emerging role of lncRNAs in osteoarthritis development and potential therapy.

Zhang X, Liu Q, Zhang J, Song C, Han Z, Wang J Front Genet. 2023; 14:1273933.

PMID: 37779916 PMC: 10538550. DOI: 10.3389/fgene.2023.1273933.

The regulatory activities of MALAT1 in the development of bone and cartilage diseases.

Zhang D, Xue J, Peng F Front Endocrinol (Lausanne). 2022; 13:1054827.

PMID: 36452326 PMC: 9701821. DOI: 10.3389/fendo.2022.1054827.

Emerging role of lncRNAs in osteoarthritis: An updated review.

Wang R, Shiu H, Lee W Front Immunol. 2022; 13:982773.

PMID: 36304464 PMC: 9593085. DOI: 10.3389/fimmu.2022.982773.

The non-coding RNA interactome in joint health and disease.

Ali S, Peffers M, Ormseth M, Jurisica I, Kapoor M Nat Rev Rheumatol. 2021; 17(11):692-705.

PMID: 34588660 DOI: 10.1038/s41584-021-00687-y.

LncRNAs as a new regulator of chronic musculoskeletal disorder.

Huang H, Xing D, Zhang Q, Li H, Lin J, He Z Cell Prolif. 2021; 54(10):e13113.

PMID: 34498342 PMC: 8488571. DOI: 10.1111/cpr.13113.

References

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

Che W, Dong Y, Quan H . RANKL inhibits cell proliferation by regulating MALAT1 expression in a human osteoblastic cell line hFOB 1.19. Cell Mol Biol (Noisy-le-grand). 2015; 61(1):7-14. View

Barr A, Campbell T, Hopkinson D, Kingsbury S, Bowes M, Conaghan P . A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis. Arthritis Res Ther. 2015; 17:228. PMC: 4548899. DOI: 10.1186/s13075-015-0735-x. View

Pearson M, Jones S . Review: Long Noncoding RNAs in the Regulation of Inflammatory Pathways in Rheumatoid Arthritis and Osteoarthritis. Arthritis Rheumatol. 2016; 68(11):2575-2583. PMC: 5347907. DOI: 10.1002/art.39759. View

Wang Q, Yang Q, Chen G, Du Z, Ren M, Wang A . LncRNA expression profiling of BMSCs in osteonecrosis of the femoral head associated with increased adipogenic and decreased osteogenic differentiation. Sci Rep. 2018; 8(1):9127. PMC: 6002551. DOI: 10.1038/s41598-018-27501-2. View

Wijesinghe S, Nicholson T, Tsintzas K, Jones S . Involvements of long noncoding RNAs in obesity-associated inflammatory diseases. Obes Rev. 2020; 22(4):e13156. DOI: 10.1111/obr.13156. View

Khalil A, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D . Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009; 106(28):11667-72. PMC: 2704857. DOI: 10.1073/pnas.0904715106. View

Yi J, Liu D, Xiao J . LncRNA MALAT1 sponges miR-30 to promote osteoblast differentiation of adipose-derived mesenchymal stem cells by promotion of Runx2 expression. Cell Tissue Res. 2018; 376(1):113-121. DOI: 10.1007/s00441-018-2963-2. View

Li X, Ellman M, Muddasani P, Wang J, Cs-Szabo G, van Wijnen A . Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis. Arthritis Rheum. 2009; 60(2):513-23. PMC: 2659545. DOI: 10.1002/art.24258. View

10.

Vincent C, Findlay D, Welldon K, Wijenayaka A, Zheng T, Haynes D . Pro-inflammatory cytokines TNF-related weak inducer of apoptosis (TWEAK) and TNFalpha induce the mitogen-activated protein kinase (MAPK)-dependent expression of sclerostin in human osteoblasts. J Bone Miner Res. 2009; 24(8):1434-49. DOI: 10.1359/jbmr.090305. View

11.

Xiao X, Zhou T, Guo S, Guo C, Zhang Q, Dong N . LncRNA MALAT1 sponges miR-204 to promote osteoblast differentiation of human aortic valve interstitial cells through up-regulating Smad4. Int J Cardiol. 2017; 243:404-412. DOI: 10.1016/j.ijcard.2017.05.037. View

12.

Hawker G . Osteoarthritis is a serious disease. Clin Exp Rheumatol. 2019; 37 Suppl 120(5):3-6. View

13.

Tonge D, Pearson M, Jones S . The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics. Osteoarthritis Cartilage. 2014; 22(5):609-21. DOI: 10.1016/j.joca.2014.03.004. View

14.

Philp A, Collier R, Grover L, Davis E, Jones S . Resistin promotes the abnormal Type I collagen phenotype of subchondral bone in obese patients with end stage hip osteoarthritis. Sci Rep. 2017; 7(1):4042. PMC: 5481425. DOI: 10.1038/s41598-017-04119-4. View

15.

Philp A, Davis E, Jones S . Developing anti-inflammatory therapeutics for patients with osteoarthritis. Rheumatology (Oxford). 2016; 56(6):869-881. DOI: 10.1093/rheumatology/kew278. View

16.

Roux B, Heward J, Donnelly L, Jones S, Lindsay M . Catalog of Differentially Expressed Long Non-Coding RNA following Activation of Human and Mouse Innate Immune Response. Front Immunol. 2017; 8:1038. PMC: 5581803. DOI: 10.3389/fimmu.2017.01038. View

17.

Zhu J, Zhang X, Gao W, Hu H, Wang X, Hao D . lncRNA/circRNA‑miRNA‑mRNA ceRNA network in lumbar intervertebral disc degeneration. Mol Med Rep. 2019; 20(4):3160-3174. PMC: 6755180. DOI: 10.3892/mmr.2019.10569. View

18.

Silva A, Moura S, Teixeira J, Barbosa M, Santos S, Almeida M . Long noncoding RNAs: a missing link in osteoporosis. Bone Res. 2019; 7:10. PMC: 6437190. DOI: 10.1038/s41413-019-0048-9. View

19.

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

20.

Suri S, Gill S, Massena de Camin S, Wilson D, McWilliams D, Walsh D . Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. Ann Rheum Dis. 2007; 66(11):1423-8. PMC: 2111605. DOI: 10.1136/ard.2006.063354. View