Osteogenic Differentiation of Renal Interstitial Fibroblasts Promoted by LncRNA May Partially Contribute to Randall's Plaque Formation

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 Jan 28

PMID 33505960

Citations 15

Authors

Zewu Zhu

Fang Huang

Weiping Xia

Huimin Zeng

Meng Gao

Yongchao Li

Feng Zeng

Cheng He

Jinbo Chen

Zhiyong Chen

Yang Li

Yu Cui

Hequn Chen

Affiliations

Soon will be listed here.

Abstract

Background: The current belief is that Randall's plaques (RP) constitute a nidus for the formation of idiopathic calcium oxalate stones, but the upstream events in RP formation remain unclear. The present study aimed to investigate whether RP formation shares similarities with biomineralization and to illustrate the potential role played by the lncRNA in osteogenic differentiation of human renal interstitial fibroblasts (hRIFs).

Materials And Methods: Biomineralization and expression were assessed in RP, and hRIFs were isolated and induced under osteogenic conditions for further experiments. The transcription initiation and termination sites in were identified by 5' and 3' RACE. RNA immunoprecipitation assays and luciferase assays were used to validate the interactions among , and miRNAs.

Results: Upregulated expression of osteogenic markers and was observed in RP and hRIFs induced with osteogenic medium. Biomineralization in RP and calcium phosphate (CaP) deposits in induced hRIFs were further verified by electron microscopy. Furthermore, overexpression of promoted the osteogenic phenotype of hRIFs, while treatment with a miR-320a-5p mimic and knockdown of significantly suppressed the osteogenic phenotype. Further analysis showed that functioned as a competing endogenous RNA to sponge miR-320a-5p, leading to upregulation of Runx2 and thus promoting osteogenic differentiation of hRIFs.

Conclusion: Ectopic calcification and partially contributed to the formation of RP, in which might promote Runx2 expression to regulate osteogenic differentiation of hRIFs by sponging miRNA-320a-5p. The current study sheds new light on the lncRNA-directed mechanism of RP formation via a process driven by osteogenic-like cells.

Citing Articles

Expression of osteogenic proteins in kidneys of cats with nephrocalcinosis.

Hengtrakul N, Furrow E, Borofsky M, Toth F, Lulich J J Vet Intern Med. 2025; 39(1):e17278.

PMID: 39757788 PMC: 11702495. DOI: 10.1111/jvim.17278.

Noncoding RNA, friend or foe for nephrolithiasis?.

Wang Q, Yang Z, Chen X, Yang Y, Jiang K Front Cell Dev Biol. 2024; 12:1457319.

PMID: 39633711 PMC: 11614778. DOI: 10.3389/fcell.2024.1457319.

Expression profiles of urine exosomal tRNA-derived small RNAs and their potential roles in calcium oxalate stone disease.

Hong S, Miao L, Yang Y, Wang S Ann Med Surg (Lond). 2024; 86(10):5802-5810.

PMID: 39359758 PMC: 11444539. DOI: 10.1097/MS9.0000000000002563.

Wilms tumor 1-associated protein mediated m6A modification promotes osteogenic differentiation of stem cells from human exfoliated deciduous teeth.

Gao W, Miao X, Xu T J Dent Sci. 2024; 19(4):2305-2314.

PMID: 39347097 PMC: 11437296. DOI: 10.1016/j.jds.2024.02.022.

Osteogenic-Like Microenvironment of Renal Interstitium Induced by Osteomodulin Contributes to Randall's Plaque Formation.

Zhu Z, Huang F, Gao M, Liu M, Zhang Y, Tang L Adv Sci (Weinh). 2024; 11(40):e2405875.

PMID: 39225583 PMC: 11516157. DOI: 10.1002/advs.202405875.

References

Mezzabotta F, Cristofaro R, Ceol M, Del Prete D, Priante G, Familiari A . Spontaneous calcification process in primary renal cells from a medullary sponge kidney patient harbouring a GDNF mutation. J Cell Mol Med. 2015; 19(4):889-902. PMC: 4395202. DOI: 10.1111/jcmm.12514. View

Morgan M, Pearle M . Medical management of renal stones. BMJ. 2016; 352:i52. DOI: 10.1136/bmj.i52. View

Kumar V, Farell G, Yu S, Harrington S, Fitzpatrick L, Rzewuska E . Cell biology of pathologic renal calcification: contribution of crystal transcytosis, cell-mediated calcification, and nanoparticles. J Investig Med. 2006; 54(7):412-24. DOI: 10.2310/6650.2006.06021. View

Hsi R, Ramaswamy K, Ho S, Stoller M . The origins of urinary stone disease: upstream mineral formations initiate downstream Randall's plaque. BJU Int. 2016; 119(1):177-184. PMC: 5161725. DOI: 10.1111/bju.13555. View

Gao Y, Xiao F, Wang C, Wang C, Cui P, Zhang X . Long noncoding RNA MALAT1 promotes osterix expression to regulate osteogenic differentiation by targeting miRNA-143 in human bone marrow-derived mesenchymal stem cells. J Cell Biochem. 2018; 119(8):6986-6996. DOI: 10.1002/jcb.26907. View

Sharpe C, Dockrell M . Primary culture of human renal proximal tubule epithelial cells and interstitial fibroblasts. Methods Mol Biol. 2011; 806:175-85. DOI: 10.1007/978-1-61779-367-7_12. View

Sabatini F, Petecchia L, Tavian M, Jodon de Villeroche V, Rossi G, Brouty-Boye D . Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Invest. 2005; 85(8):962-71. DOI: 10.1038/labinvest.3700300. View

Xiao W, Gu X, Hu B, Liu X, Zi Y, Li M . Role of microRNA-129-5p in osteoblast differentiation from bone marrow mesenchymal stem cells. Cell Mol Biol (Noisy-le-grand). 2016; 62(3):95-9. 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

10.

V Wiener S, Chen L, Shimotake A, Kang M, Stoller M, Ho S . Novel insights into renal mineralization and stone formation through advanced imaging modalities. Connect Tissue Res. 2018; 59(sup1):102-110. PMC: 6120852. DOI: 10.1080/03008207.2017.1409219. View

11.

Canales B, Hatch M . Kidney stone incidence and metabolic urinary changes after modern bariatric surgery: review of clinical studies, experimental models, and prevention strategies. Surg Obes Relat Dis. 2014; 10(4):734-42. PMC: 4167184. DOI: 10.1016/j.soard.2014.03.026. View

12.

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

13.

Kapranov P, Cheng J, Dike S, Nix D, Duttagupta R, Willingham A . RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. 2007; 316(5830):1484-8. DOI: 10.1126/science.1138341. View

14.

Priante G, Mezzabotta F, Cristofaro R, Quaggio F, Ceol M, Gianesello L . Cell death in ectopic calcification of the kidney. Cell Death Dis. 2019; 10(6):466. PMC: 6565680. DOI: 10.1038/s41419-019-1697-8. View

15.

Gay C, Letavernier E, Verpont M, Walls M, Bazin D, Daudon M . Nanoscale Analysis of Randall's Plaques by Electron Energy Loss Spectromicroscopy: Insight in Early Biomineral Formation in Human Kidney. ACS Nano. 2020; 14(2):1823-1836. DOI: 10.1021/acsnano.9b07664. View

16.

Peng S, Cao L, He S, Zhong Y, Ma H, Zhang Y . An Overview of Long Noncoding RNAs Involved in Bone Regeneration from Mesenchymal Stem Cells. Stem Cells Int. 2018; 2018:8273648. PMC: 5829309. DOI: 10.1155/2018/8273648. View

17.

Zhang C, Yuan J, Hu H, Chen W, Liu M, Zhang J . Long non-coding RNA CHCHD4P4 promotes epithelial-mesenchymal transition and inhibits cell proliferation in calcium oxalate-induced kidney damage. Braz J Med Biol Res. 2017; 51(1):e6536. PMC: 5685061. DOI: 10.1590/1414-431X20176536. View

18.

Khan S, Canales B . Unified theory on the pathogenesis of Randall's plaques and plugs. Urolithiasis. 2014; 43 Suppl 1:109-23. PMC: 4373525. DOI: 10.1007/s00240-014-0705-9. View

19.

Liu H, Ye T, Yang X, Liu J, Jiang K, Lu H . H19 promote calcium oxalate nephrocalcinosis-induced renal tubular epithelial cell injury via a ceRNA pathway. EBioMedicine. 2019; 50:366-378. PMC: 6921206. DOI: 10.1016/j.ebiom.2019.10.059. View

20.

Liu K, Huang J, Ni J, Song D, Ding M, Wang J . MALAT1 promotes osteosarcoma development by regulation of HMGB1 via miR-142-3p and miR-129-5p. Cell Cycle. 2017; 16(6):578-587. PMC: 5384591. DOI: 10.1080/15384101.2017.1288324. View