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RETRACTED ARTICLE: Baicalin augments the differentiation of osteoblasts via enhancement of microRNA-217

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This article was retracted on 29 February 2024

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Abstract

Baicalin (BAI), a sort of flavonoid monomer, acquires from Scutellaria baicalensis Georgi, which was forcefully reported in diversified ailments due to the pleiotropic properties. But, the functions of BAI in osteoblast differentiation have not been addressed. The intentions of this study are to attest the influences of BAI in the differentiation of osteoblasts. MC3T3-E1 cells or rat primary osteoblasts were exposed to BAI, and then cell viability, ALP activity, mineralization process, and Runx2 and Ocn expression were appraised through implementing CCK-8, p-nitrophenyl phosphate (pNPP), Alizarin red staining, western blot, and RT-qPCR assays. The microRNA-217 (miR-217) expression was evaluated in MC3T3-E1 cells or rat primary osteoblasts after BAI disposition; meanwhile, the functions of miR-217 in BAI-administrated MC3T3-E1 cells were estimated after miR-217 inhibitor transfection. The impacts of BAI and miR-217 inhibition on Wnt/β-catenin and MEK/ERK pathways were probed to verify the involvements in BAI-regulated the differentiation of osteoblasts. BAI accelerated cell viability, osteoblast activity, and Runx2 and Ocn expression in MC3T3-E1 cells or rat primary osteoblasts, and the phenomena were mediated via activations of Wnt/β-catenin and MEK/ERK pathways. Elevation of miR-217 was observed in BAI-disposed MC3T3-E1 cells or rat primary osteoblasts, and miR-217 repression annulled the functions of BAI in MC3T3-E1 cell viability and differentiation. Additionally, the activations of Wnt/β-catenin and MEK/ERK pathways evoked by BAI were both restrained by repression of miR-217. These explorations uncovered that BAI augmented the differentiation of osteoblasts via activations of Wnt/β-catenin and MEK/ERK pathways by ascending miR-217 expression.

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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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References

  1. Meinberg EG, Agel J, Roberts CS, Karam MD, Kellam JF (2018) Fracture and dislocation classification compendium—2018. J Orthop Trauma 32(Suppl 1):S1–S170. https://doi.org/10.1097/bot.0000000000001063

    Article  PubMed  Google Scholar 

  2. Tsuda T (2017) Epidemiology of fragility fractures and fall prevention in the elderly: a systematic review of the literature. Curr Orthop Pract 28(6):580–585. https://doi.org/10.1097/BCO.0000000000000563

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bonafede M, Espindle D, Bower AG (2013) The direct and indirect costs of long bone fractures in a working age US population. J Med Econ 16(1):169–178. https://doi.org/10.3111/13696998.2012.737391

    Article  PubMed  Google Scholar 

  4. Hwang K, Ki SJ, Ko SH (2017) Etiology of nasal bone fractures. J Craniofac Surg 28(3):785–788

    Article  PubMed  Google Scholar 

  5. Kilicarslan K, Bektaser B, Ucguder A, Dogan M, Ugurlu M, Yildirim H (2011) Results of early surgical treatment of intra-articular complex fractures of the humerus in adults. Bratisl lek listy 112(9):501–505

    CAS  PubMed  Google Scholar 

  6. Moon S-H, Kim H-S, Jung S-N, Kwon H (2016) The efficacy of transverse fixation and early exercise in the treatment of fourth metacarpal bone fractures. Arch Plast Surg 43(2):189–196. https://doi.org/10.5999/aps.2016.43.2.189

    Article  PubMed  PubMed Central  Google Scholar 

  7. Jeong SJ, Jeong MJ (2016) Effect of thymosin beta4 on the differentiation and mineralization of MC3T3-E1 cell on a titanium surface. J Nanosci Nanotechnol 16(2):1979–1983

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  8. Zhang J, Zhang H, Deng X, Zhang Y, Xu K (2017) Baicalin protects AML-12 cells from lipotoxicity via the suppression of ER stress and TXNIP/NLRP3 inflammasome activation. Chem Biol Interact 278:189–196. https://doi.org/10.1016/j.cbi.2017.10.010

    Article  CAS  PubMed  Google Scholar 

  9. Lai W, Jia J, Yan B, Jiang Y, Shi Y, Chen L, Mao C, Liu X, Tang H, Gao M, Cao Y, Liu S, Tao Y (2017) Baicalin hydrate inhibits cancer progression in nasopharyngeal carcinoma by affecting genome instability and splicing. Oncotarget 9(1):901–914. https://doi.org/10.18632/oncotarget.22868

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lin D, Du Q, Wang H, Gao G, Zhou J, Ke L, Chen T, Shaw C, Rao P (2017) Antidiabetic micro-/nanoaggregates from ge-gen-qin-lian-tang decoction increase absorption of baicalin and cellular antioxidant activity in vitro. Biomed Res Int 2017:9217912. https://doi.org/10.1155/2017/9217912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xu Z, Wang F, Tsang SY, Ho KH, Zheng H, Yuen CT, Chow CY, Xue H (2006) Anxiolytic-like effect of baicalin and its additivity with other anxiolytics. Planta Med 72(2):189–192. https://doi.org/10.1055/s-2005-873193

    Article  CAS  PubMed  Google Scholar 

  12. Dinda B, Dinda S, DasSharma S, Banik R, Chakraborty A, Dinda M (2017) Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur J Med Chem 131:68–80. https://doi.org/10.1016/j.ejmech.2017.03.004

    Article  CAS  PubMed  Google Scholar 

  13. Moghaddam E, Teoh BT, Sam SS, Lani R, Hassandarvish P, Chik Z, Yueh A, Abubakar S, Zandi K (2014) Baicalin, a metabolite of baicalein with antiviral activity against dengue virus. Sci Rep 4:5452. https://doi.org/10.1038/srep05452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kim JY, Lee JI, Song M, Lee D, Song J, Kim SY, Park J, Choi HY, Kim H (2015) Effects of Eucommia ulmoides extract on longitudinal bone growth rate in adolescent female rats. PTR 29(1):148–153. https://doi.org/10.1002/ptr.5195

    Article  PubMed  Google Scholar 

  15. Lu L, Rao L, Jia H, Chen J, Lu X, Yang G, Li Q, Lee KKH, Yang L (2017) Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling. J Cell Mol Med 21(7):1361–1372. https://doi.org/10.1111/jcmm.13066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wu X, Zhi F, Lun W, Deng Q, Zhang W (2018) Baicalin inhibits PDGF-BB-induced hepatic stellate cell proliferation, apoptosis, invasion, migration and activation via the miR-3595/ACSL4 axis. Int J Mol Med 41(4):1992–2002. https://doi.org/10.3892/ijmm.2018.3427

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wang L, Zhang R, Chen J, Wu Q, Kuang Z (2017) Baicalin protects against TNF-alpha-induced injury by down-regulating miR-191a that targets the tight junction protein ZO-1 in IEC-6 cells. Biol Pharm Bull 40(4):435–443. https://doi.org/10.1248/bpb.b16-00789

    Article  CAS  PubMed  Google Scholar 

  18. Wei R, Deng Z, Su J (2015) miR-217 targeting Wnt5a in osteosarcoma functions as a potential tumor suppressor. Biomed Pharmacother 72:158–164. https://doi.org/10.1016/j.biopha.2015.04.012

    Article  CAS  PubMed  Google Scholar 

  19. Su J, Wang Q, Liu Y, Zhong M (2014) miR-217 inhibits invasion of hepatocellular carcinoma cells through direct suppression of E2F3. Mol Cell Biochem 392(1–2):289–296. https://doi.org/10.1007/s11010-014-2039-x

    Article  CAS  PubMed  Google Scholar 

  20. Zhu YL, Wang S, Ding DG, Xu L, Zhu HT (2017) miR217 inhibits osteogenic differentiation of rat bone marrowderived mesenchymal stem cells by binding to Runx2. Mol Med Rep 15(5):3271–3277. https://doi.org/10.3892/mmr.2017.6349

    Article  CAS  PubMed  Google Scholar 

  21. Peng Y, Fu Z-Z, Guo C-S, Zhang Y-X, Di Y, Jiang B, Li Q-W (2015) Effects and mechanism of baicalin on apoptosis of cervical cancer HeLa cells in vitro. IJPR 14(1):251–261

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  23. Guo AJ, Choi RC, Cheung AW, Chen VP, Xu SL, Dong TT, Chen JJ, Tsim KW (2011) Baicalin, a flavone, induces the differentiation of cultured osteoblasts: an action via the Wnt/beta-catenin signaling pathway. J Biol Chem 286(32):27882–27893. https://doi.org/10.1074/jbc.M111.236281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Noguchi T, Ebina K, Hirao M, Otsuru S, Guess AJ, Kawase R, Ohama T, Yamashita S, Etani Y, Okamura G, Yoshikawa H (2018) Apolipoprotein E plays crucial roles in maintaining bone mass by promoting osteoblast differentiation via ERK1/2 pathway and by suppressing osteoclast differentiation via c-Fos, NFATc1, and NF-kappaB pathway. Biochem Biophys Res Commun 503(2):644–650. https://doi.org/10.1016/j.bbrc.2018.06.055

    Article  CAS  PubMed  Google Scholar 

  25. Feng G, Zhang J, Feng X, Wu S, Huang D, Hu J, Zhu S, Song D (2016) Runx2 modified dental pulp stem cells (DPSCs) enhance new bone formation during rapid distraction osteogenesis (DO). Differ Res Biol Divers 92(4):195–203. https://doi.org/10.1016/j.diff.2016.06.001

    Article  CAS  Google Scholar 

  26. Bustos F, Sepúlveda H, Prieto CP, Carrasco M, Díaz L, Palma J, Lattus J, Montecino M, Palma V (2017) RUNX2 induction during differentiation of Wharton’s jelly mesenchymal stem cells to osteoblasts is regulated by JARID1B histone demethylase. Stem Cells (Dayton, Ohio) 35(12):2430–2441

    Article  PubMed  Google Scholar 

  27. Al Rifai O, Chow J, Lacombe J, Julien C, Faubert D, Susan-Resiga D, Essalmani R, Creemers JW, Seidah NG, Ferron M (2017) Proprotein convertase furin regulates osteocalcin and bone endocrine function. J Clin Investig 127(11):4104–4117. https://doi.org/10.1172/jci93437

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kang IH, Jeong BC, Hur SW, Choi H, Choi SH, Ryu JH, Hwang YC, Koh JT (2015) MicroRNA-302a stimulates osteoblastic differentiation by repressing COUP-TFII expression. J Cell Physiol 230(4):911–921. https://doi.org/10.1002/jcp.24822

    Article  CAS  PubMed  Google Scholar 

  29. Mai ZH, Peng ZL, Zhang JL, Chen L, Liang HY, Cai B, Ai H (2013) miRNA expression profile during fluid shear stress-induced osteogenic differentiation in MC3T3-E1 cells. Chin Med J 126(8):1544–1550

    Article  CAS  PubMed  Google Scholar 

  30. Shan Z, Cheng N, Huang R, Zhao B, Zhou Y (2018) Puerarin promotes the proliferation and differentiation of MC3T3-E1 cells via microRNA-106b by targeting receptor activator of nuclear factor-kappaB ligand. Exp Ther Med 15(1):55–60. https://doi.org/10.3892/etm.2017.5405

    Article  CAS  PubMed  Google Scholar 

  31. Huang Z, Cheng C, Wang J, Liu X, Wei H, Han Y, Yang S, Wang X (2018) Icariin regulates the osteoblast differentiation and cell proliferation of MC3T3-E1 cells through microRNA-153 by targeting Runt-related transcription factor 2. Exp Ther Med 15(6):5159–5166. https://doi.org/10.3892/etm.2018.6127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhu H, Hou L, Liu J, Li Z (2016) MiR-217 is down-regulated in psoriasis and promotes keratinocyte differentiation via targeting GRHL2. Biochem Biophys Res Commun 471(1):169–176. https://doi.org/10.1016/j.bbrc.2016.01.157

    Article  CAS  PubMed  Google Scholar 

  33. Zhang Y, Xie RL, Croce CM, Stein JL, Lian JB, van Wijnen AJ, Stein GS (2011) A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci USA 108(24):9863–9868. https://doi.org/10.1073/pnas.1018493108

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  34. Fei Y, Xiao L, Doetschman T, Coffin DJ, Hurley MM (2011) Fibroblast growth factor 2 stimulation of osteoblast differentiation and bone formation is mediated by modulation of the Wnt signaling pathway. J Biol Chem 286(47):40575–40583. https://doi.org/10.1074/jbc.M111.274910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kim MB, Song Y, Hwang JK (2014) Kirenol stimulates osteoblast differentiation through activation of the BMP and Wnt/beta-catenin signaling pathways in MC3T3-E1 cells. Fitoterapia 98:59–65. https://doi.org/10.1016/j.fitote.2014.07.013

    Article  CAS  PubMed  Google Scholar 

  36. Guo C, Yang RJ, Jang K, Zhou XL, Liu YZ (2017) Protective effects of pretreatment with quercetin against lipopolysaccharide-induced apoptosis and the inhibition of osteoblast differentiation via the MAPK and Wnt/beta-catenin pathways in MC3T3-E1 Cells. Cell Physiol Biochem 43(4):1547–1561. https://doi.org/10.1159/000481978

    Article  CAS  PubMed  Google Scholar 

  37. Zhai F, Song N, Ma J, Gong W, Tian H, Li X, Jiang C, Wang H (2017) FGF18 inhibits MC3T3E1 cell osteogenic differentiation via the ERK signaling pathway. Mol Med Rep 16(4):4127–4132. https://doi.org/10.3892/mmr.2017.7088

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Longzhan Xiang.

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This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s11010-024-04980-8

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Supplementary Figure 1

BAI expedited rat primary osteoblast viability and osteogenic differentiation. After BAI management (20, 50, and 100 μM), (A) CCK-8 assay for rat primary osteoblast viability evaluation; (B) p-nitrophenyl phosphate (pNPP) assay for ALP activity detection; (C) western blot assay for Runx2 and Ocn protein level estimation; (D and E) RT-qPCR assay for Runx2 and Ocn mRNA expression level determination. *P < 0.05, **P < 0.01, ***P < 0.001 (TIFF 641 kb)

Supplementary Figure 2

BAI promoted osteoblast activity. After BAI management (20, 50, and 100 μM, TRAP activity assay for mature osteoclasts evaluation in (A) MC3T3-E1 cells and (B) rat primary osteoblasts. **P < 0.01, ***P < 0.001 (TIFF 252 kb)

Supplementary Figure 3

BAI expedited the activations of Wnt/β-catenin and MEK/ERK pathways in rat primary osteoblasts. After BAI administration (20, 50, and 100 μM), (A and B) western blot assay for wnt3a and β-catenin protein level measurement; (C and D) western blot assay for p/t-MEK and p/t-ERK protein level determination. *P < 0.05, **P < 0.01 (TIFF 1437 kb)

Supplementary Figure 4

Enhancement of miR-217 was triggered by BAI in rat primary osteoblasts. After BAI management (20, 50, and 100 μM), RT-qPCR assay for the expression level of miR-217 evaluation in rat primary osteoblasts. *P < 0.05, **P < 0.01 (TIFF 171 kb)

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Wang, Q., Shi, D., Geng, Y. et al. RETRACTED ARTICLE: Baicalin augments the differentiation of osteoblasts via enhancement of microRNA-217. Mol Cell Biochem 463, 91–100 (2020). https://doi.org/10.1007/s11010-019-03632-6

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