Top

Journal of Orthopaedic Surgery and Research

Published in:

Open Access 01-12-2024 | Research article

CircPRKD3/miR-6783-3p responds to mechanical force to facilitate the osteogenesis of stretched periodontal ligament stem cells

Authors: Jiani Liu, Rui Liu, Hong Wang, Zijie Zhang, Jixiao Wang, Fulan Wei

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2024

Abstract

Background

The mechanotransduction mechanisms by which cells regulate tissue remodeling are not fully deciphered. Circular RNAs (circRNAs) are crucial to various physiological processes, including cell cycle, differentiation, and polarization. However, the effects of mechanical force on circRNAs and the role of circRNAs in the mechanobiology of differentiation and remodeling in stretched periodontal ligament stem cells (PDLSCs) remain unclear. This article aims to explore the osteogenic function of mechanically sensitive circular RNA protein kinase D3 (circPRKD3) and elucidate its underlying mechanotransduction mechanism.

Materials and methods

PDLSCs were elongated with 8% stretch at 0.5 Hz for 24 h using the Flexcell® FX-6000™ Tension System. CircPRKD3 was knockdown or overexpressed with lentiviral constructs or plasmids. The downstream molecules of circPRKD3 were predicted by bioinformatics analysis. The osteogenic effect of related molecules was evaluated by quantitative real-time PCR (qRT‐PCR) and western blot.

Results

Mechanical force enhanced the osteogenesis of PDLSCs and increased the expression of circPRKD3. Knockdown of circPRKD3 hindered PDLSCs from osteogenesis under mechanical force, while overexpression of circPRKD3 promoted the early osteogenesis process of PDLSCs. With bioinformatics analysis and multiple software predictions, we identified hsa-miR-6783-3p could act as the sponge of circPRKD3 to indirectly regulate osteogenic differentiation of mechanically stimulated PDLSCs.

Conclusions

Our results first suggested that both circPRKD3 and hsa-miR-6783-3p could enhance osteogenesis of stretched PDLSCs. Furthermore, hsa-miR-6783-3p could sponge circPRKD3 to indirectly regulate RUNX2 during the periodontal tissue remodeling process in orthodontic treatment.

Available only for authorised users

Li M, Zhang C, Yang Y. Effects of mechanical forces on osteogenesis and osteoclastogenesis in human periodontal ligament fibroblasts: a systematic review of in vitro studies. Bone Joint Res. 2019;8(1):19–31.PubMedPubMedCentralCrossRef

Jin SS, He DQ, Wang Y, Zhang T, Yu HJ, Li ZX, et al. Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4. Cell Prolif. 2020;53(10):e12912.PubMedPubMedCentralCrossRef

Liu M, Zhang H, Li Y, Wang S. Noncoding RNAs interplay in Ovarian Cancer Therapy and Drug Resistance. Cancer biotherapy & radiopharmaceuticals; 2022.

Amorim M, Salta S, Henrique R, Jerónimo C. Decoding the usefulness of non-coding RNAs as breast cancer markers. J Translational Med. 2016;14:265.CrossRef

Ali T, Grote P. Beyond the RNA-dependent function of LncRNA genes. eLife. 2020;9.

Warner WA, Spencer DH, Trissal M, White BS, Helton N, Ley TJ, et al. Expression profiling of snoRNAs in normal hematopoiesis and AML. Blood Adv. 2018;2(2):151–63.PubMedPubMedCentralCrossRef

Xie X, Guo P, Yu H, Wang Y, Chen G. Ribosomal proteins: insight into molecular roles and functions in hepatocellular carcinoma. Oncogene. 2018;37(3):277–85.PubMedCrossRef

Ghafouri-Fard S, Poulet C, Malaise M, Abak A, Mahmud Hussen B, Taheriazam A, et al. The emerging role of non-coding RNAs in Osteoarthritis. Front Immunol. 2021;12:773171.PubMedPubMedCentralCrossRef

Tan YT, Lin JF, Li T, Li JJ, Xu RH, Ju HQ. LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer. Cancer Commun (London England). 2021;41(2):109–20.CrossRef

10.

Li M, Zhang Z, Gu X, Jin Y, Feng C, Yang S, et al. MicroRNA-21 affects mechanical force-induced midpalatal suture remodelling. Cell Prolif. 2020;53(1):e12697.PubMedCrossRef

11.

Zhang Z, He Q, Yang S, Zhao X, Li X, Wei F. Mechanical force-sensitive lncRNA SNHG8 inhibits osteogenic differentiation by regulating EZH2 in hPDLSCs. Cell Signal. 2022;93:110285.PubMedCrossRef

12.

Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–8.PubMedCrossRef

13.

Wang H, Feng C, Jin Y, Tan W, Wei F. Identification and characterization of circular RNAs involved in mechanical force-induced periodontal ligament stem cells. J Cell Physiol. 2019;234(7):10166–77.PubMedCrossRef

14.

Zhong W, Li X, Pathak JL, Chen L, Cao W, Zhu M, et al. Dicalcium silicate microparticles modulate the differential expression of circRNAs and mRNAs in BMSCs and promote osteogenesis via circ_1983-miR-6931-Gas7 interaction. Biomaterials Sci. 2020;8(13):3664–77.CrossRef

15.

Gu X, Li M, Jin Y, Liu D, Wei F. Identification and integrated analysis of differentially expressed lncRNAs and circRNAs reveal the potential ceRNA networks during PDLSC osteogenic differentiation. BMC Genet. 2017;18(1):100.PubMedPubMedCentralCrossRef

16.

Wei F, Liu D, Feng C, Zhang F, Yang S, Hu Y, et al. microRNA-21 mediates stretch-induced osteogenic differentiation in human periodontal ligament stem cells. Stem Cells Dev. 2015;24(3):312–9.PubMedCrossRef

17.

Liu Y, Zhou Y, Ma X, Chen L. Inhibition lysosomal degradation of Clusterin by protein kinase D3 promotes triple-negative breast Cancer Tumor Growth. Advanced science (Weinheim, Baden-Wurttemberg. Germany). 2021;8(4):2003205.

18.

Zhang S, Liu H, Yin M, Pei X, Hausser A, Ishikawa E, et al. Deletion of protein kinase D3 promotes liver fibrosis in mice. Hepatology (Baltimore MD). 2020;72(5):1717–34.PubMedCrossRef

19.

Baker J, Falconer AMD, Wilkinson DJ, Europe-Finner GN, Litherland GJ, Rowan AD. Protein kinase D3 modulates MMP1 and MMP13 expression in human chondrocytes. PLoS ONE. 2018;13(4):e0195864.PubMedPubMedCentralCrossRef

20.

Leightner AC, Mello Guimaraes Meyers C, Evans MD, Mansky KC, Gopalakrishnan R, Jensen ED. Regulation of Osteoclast differentiation at multiple stages by protein kinase D Family Kinases. Int J Mol Sci. 2020;21(3).

21.

He Q, Yang S, Gu X, Li M, Wang C, Wei F. Long noncoding RNA TUG1 facilitates osteogenic differentiation of periodontal ligament stem cells via interacting with Lin28A. Cell Death Dis. 2018;9(5):455.PubMedPubMedCentralCrossRef

22.

Liu J, Wang H, Zhang L, Li X, Ding X, Ding G et al. Periodontal ligament stem cells promote polarization of M2 macrophages. J Leukoc Biol. 2022.

23.

Kefauver JM, Ward AB, Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels. Nature. 2020;587(7835):567–76.PubMedPubMedCentralCrossRef

24.

Sasaki F, Hayashi M, Ono T, Nakashima T. The regulation of RANKL by mechanical force. J Bone Miner Metab. 2021;39(1):34–44.PubMedCrossRef

25.

Jeon HH, Teixeira H, Tsai A. Mechanistic insight into Orthodontic Tooth Movement Based on Animal Studies: a critical review. J Clin Med. 2021;10(8).

26.

Raisz LG. Physiology and pathophysiology of bone remodeling. Clin Chem. 1999;45(8 Pt 2):1353–8.PubMed

27.

Chaushu S, Klein Y, Mandelboim O, Barenholz Y, Fleissig O. Immune Changes Induced by Orthodontic Forces: a critical review. J Dent Res. 2022;101(1):11–20.PubMedCrossRef

28.

Yu W, Chen C, Kou X, Sui B, Yu T, Liu D, et al. Mechanical force-driven TNFα endocytosis governs stem cell homeostasis. Bone Res. 2021;8(1):44.PubMedPubMedCentralCrossRef

29.

Wang H, Feng C, Li M, Zhang Z, Liu J, Wei F. Analysis of lncRNAs-miRNAs-mRNAs networks in periodontal ligament stem cells under mechanical force. Oral Dis. 2020.

30.

Liu Y, Liu H, Li Y, Mao R, Yang H, Zhang Y, et al. Circular RNA SAMD4A controls adipogenesis in obesity through the miR-138-5p/EZH2 axis. Theranostics. 2020;10(10):4705–19.PubMedPubMedCentralCrossRef

31.

Yao MD, Jiang Q, Ma Y, Zhu Y, Zhang QY, Shi ZH, et al. Targeting circular RNA-MET for anti-angiogenesis treatment via inhibiting endothelial tip cell specialization. Mol Therapy: J Am Soc Gene Therapy. 2022;30(3):1252–64.CrossRef

32.

Liu C, Liu AS, Zhong D, Wang CG, Yu M, Zhang HW, et al. Circular RNA AFF4 modulates osteogenic differentiation in BM-MSCs by activating SMAD1/5 pathway through miR-135a-5p/FNDC5/Irisin axis. Cell Death Dis. 2021;12(7):631.PubMedPubMedCentralCrossRef

33.

Gu X, Li X, Jin Y, Zhang Z, Li M, Liu D, et al. CDR1as regulated by hnRNPM maintains stemness of periodontal ligament stem cells via miR-7/KLF4. J Cell Mol Med. 2021;25(9):4501–15.PubMedPubMedCentralCrossRef

34.

Li R, Jiang J, Shi H, Qian H, Zhang X, Xu W. CircRNA: a rising star in gastric cancer. Cell Mol Life Sci. 2020;77(9):1661–80.PubMedCrossRef

35.

Durand N, Borges S, Storz P. Protein Kinase D Enzymes as regulators of EMT and Cancer Cell Invasion. J Clin Med. 2016;5(2).

36.

Burciaga SD, Saavedra F, Fischer L, Johnstone K, Jensen ED. Protein kinase D3 conditional knockout impairs osteoclast formation and increases trabecular bone volume in male mice. Bone. 2023;172:116759.PubMedCrossRef

37.

Wang H, Feng C, Wang M, Yang S, Wei F. Circular RNAs: Diversity of Functions and a Regulatory Nova in oral medicine: a Pilot Review. Cell Transplant. 2019;28(7):819–30.PubMedPubMedCentralCrossRef

38.

Su L, Li R, Zhang Z, Liu J, Du J, Wei H. Identification of altered exosomal microRNAs and mRNAs in Alzheimer’s disease. Ageing Res Rev. 2022;73:101497.PubMedCrossRef

39.

Huang X, Li Z, Zhang Q, Wang W, Li B, Wang L, et al. Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression. Mol Cancer. 2019;18(1):71.PubMedPubMedCentralCrossRef

40.

Su H, Tao T, Yang Z, Kang X, Zhang X, Kang D, et al. Circular RNA cTFRC acts as the sponge of MicroRNA-107 to promote bladder carcinoma progression. Mol Cancer. 2019;18(1):27.PubMedPubMedCentralCrossRef

41.

Zhang Z, Moon R, Thorne JL, Moore JB. NAFLD and vitamin D: evidence for intersection of microRNA-regulated pathways. Nutr Res Rev. 2021:1–20.

42.

Yao Y, Hua Q, Zhou Y. CircRNA has_circ_0006427 suppresses the progression of lung adenocarcinoma by regulating miR-6783-3p/DKK1 axis and inactivating Wnt/β-catenin signaling pathway. Biochem Biophys Res Commun. 2019;508(1):37–45.PubMedCrossRef

43.

Wu KL, Tsai YM, Huang YC, Wu YY, Chang CY, Liu YW, et al. LINC02323 facilitates development of lung squamous cell carcinoma by miRNA sponge and RBP dysregulation and links to poor prognosis. Thorac cancer. 2023;14(4):407–18.PubMedCrossRef

44.

Sharma AR, Vohra M, Shukla V, Guddattu V, Razak Uk A, Shetty R, et al. Coding SNPs in hsa-mir-1343-3p and hsa-mir-6783-3p target sites of CYP2C19 modulates clopidogrel response in individuals with cardiovascular diseases. Life Sci. 2020;245:117364.PubMedCrossRef

45.

Haque S, Harries LW. Circular RNAs (circRNAs) in Health and Disease. Genes. 2017;8(12).

46.

Yang R, Xing L, Zheng X, Sun Y, Wang X, Chen J. The circRNA circAGFG1 acts as a sponge of mir-195-5p to promote triple-negative breast cancer progression through regulating CCNE1 expression. Mol Cancer. 2019;18(1):4.PubMedPubMedCentralCrossRef

47.

Li J, Huang C, Zou Y, Ye J, Yu J, Gui Y. CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p. Mol Cancer. 2020;19(1):103.PubMedPubMedCentralCrossRef

48.

Peng F, Gong W, Li S, Yin B, Zhao C, Liu W, et al. circRNA_010383 acts as a sponge for miR-135a, and its downregulated expression contributes to Renal Fibrosis in Diabetic Nephropathy. Diabetes. 2021;70(2):603–15.PubMedCrossRef

49.

Xu L, Feng X, Hao X, Wang P, Zhang Y, Zheng X, et al. CircSETD3 (Hsa_circ_0000567) acts as a sponge for microRNA-421 inhibiting hepatocellular carcinoma growth. J Experimental Clin cancer Research: CR. 2019;38(1):98.PubMedCentralCrossRef

50.

Chen LH, Wang LP, Ma XQ. Circ_SPECC1 enhances the inhibition of miR-526b on downstream KDM4A/YAP1 pathway to regulate the growth and invasion of gastric cancer cells. Biochem Biophys Res Commun. 2019;517(2):253–9.PubMedCrossRef

Title: CircPRKD3/miR-6783-3p responds to mechanical force to facilitate the osteogenesis of stretched periodontal ligament stem cells
Authors: Jiani Liu
Rui Liu
Hong Wang
Zijie Zhang
Jixiao Wang
Fulan Wei
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2024
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-024-04727-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

CircPRKD3/miR-6783-3p responds to mechanical force to facilitate the osteogenesis of stretched periodontal ligament stem cells

Abstract

Background

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2024

Clinical efficacy of greater trochanter osteotomy with tension wire fixation in total hip arthroplasty for Crowe type IV developmental dysplasia of the hip

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats

Combined Systemic Immune-inflammatory Index (SII) and Geriatric Nutritional Risk Index (GNRI) predict survival in elderly patients with hip fractures: a retrospective study

The effect of the whole-process care model of the medical union on the improvement of kinesiophobia and bone mineral density in patients with osteoporosis

Clinical effects of arthroscopic-assisted uni-portal spinal surgery and unilateral bi-portal endoscopy on unilateral laminotomy for bilateral decompression in patients with lumbar spinal stenosis: a retrospective cohort study

Proposal for a classification system of radiographic bone changes after cervical disc replacement