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ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis

  • Authors:
    • Luna Ge
    • Yazhou Cui
    • Baoyan Liu
    • Xiaoli Yin
    • Jingxiang Pang
    • Jinxiang Han
  • View Affiliations / Copyright

    Affiliations: College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China, Key Laboratory for Rare and Uncommon Diseases of Shandong Province, Shandong Medicinal Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China, School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China
    Copyright: © Ge et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3469-3476
    |
    Published online on: March 1, 2019
       https://doi.org/10.3892/mmr.2019.9999
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Abstract

Reports of the ameliorative effect of angelicin on sex hormone deficiency‑induced osteoporosis have highlighted this compound as a candidate for the treatment of osteoporosis. However, the molecular mechanisms of action of angelicin on osteoblast differentiation have not been thoroughly researched. The aim of the present study was to evaluate the effect of angelicin on the proliferation, differentiation and mineralization of rat calvarial osteoblasts using a Cell Counting Kit‑8, alkaline phosphatase activity and the expression of osteogenic genes and proteins. Treatment with angelicin promoted the proliferation, matrix mineralization and upregulation of osteogenic marker genes including collagen type I α 1 and bone γ‑carboxyglutamate in fetal rat calvarial osteoblasts. Furthermore, angelicin promoted the expression of β‑catenin and runt related transcription factor 2, which serve a vital role in the Wnt/β‑catenin signaling pathway. Consistently, the osteogenic effect of angelicin was attenuated by the use of a Wnt inhibitor. Moreover, angelicin increased the expression of estrogen receptor α (ERα), which also serves a key role in osteoblast differentiation. Taken together, these results demonstrated that angelicin may promote osteoblast differentiation through activation of ERα and the Wnt/β‑catenin signaling pathway.
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1 

Tella SH and Gallagher JC: Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol. 142:155–170. 2015. View Article : Google Scholar

2 

Hiligsmann M, Evers SM, Ben Sedrine W, Kanis JA, Ramaekers B, Reginster JY, Silverman S, Wyers CE and Boonen A: A systematic review of cost-effectiveness analyses of drugs for postmenopausal osteoporosis. Pharmacoeconomics. 33:205–224. 2014. View Article : Google Scholar

3 

Schwarz P, Jorgensen NR and Abrahamsen B: Status of drug development for the prevention and treatment of osteoporosis. Expert Opin Drug Discov. 9:245–253. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Ishikawa K, Nagai T, Sakamoto K, Ohara K, Eguro T, Ito H, Toyoshima Y, Kokaze A, Toyone T and Inagaki K: High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis. Ther Clin Risk Manag. 12:1831–1840. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Lo Russo L, Lo Muzio L, Buccelli C and Di Lorenzo P: Bisphosphonate-related osteonecrosis of the jaws: Legal liability from the perspective of the prescribing physician. J Bone Miner Metab. 31:601–603. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Mukwaya E, Xu F, Wong MS and Zhang Y: Chinese herbal medicine for bone health. Pharm Biol. 52:1223–1228. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Chopra B, Kumar A and Lal K: Psoralea corylifolia L. (Buguchi)-Folklore to modern evidence: Review. Fitoterapia. 90:44–56. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Wang YF, Liu YN, Xiong W, Yan DM, Zhu Y, Gao XM, Xu YT and Qi AD: A UPLC-MS/MS method for in vivo and in vitro pharmacokinetic studies of psoralenoside, isopsoralenoside, psoralen and isopsoralen from Psoralea corylifolia extract. J Ethnopharmacol. 151:609–617. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Wang J, Li SF, Wang T, Sun CH, Wang L, Huang MJ, Chen J, Zheng SW, Wang N, Zhang YJ and Chen TY: Isopsoralen-mediated suppression of bone marrow adiposity and attenuation of the adipogenic commitment of bone marrow-derived mesenchymal stem cells. Int J Mol Med. 39:527–538. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Yuan X, Bi Y, Yan Z, Pu W, Li Y and Zhou K: Psoralen and isopsoralen ameliorate sex hormone deficiency-induced osteoporosis in female and male mice. Biomed Res Int. 2016:68694522016. View Article : Google Scholar : PubMed/NCBI

11 

Yeh LC, Adamo ML, Kitten AM, Olson MS and Lee JC: Osteogenic protein-1-mediated insulin-like growth factor gene expression in primary cultures of rat osteoblastic cells. Endocrinology. 137:1921–1931. 1996. View Article : Google Scholar : PubMed/NCBI

12 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Neve A, Corrado A and Cantatore FP: Osteoblast physiology in normal and pathological conditions. Cell Tissue Res. 343:289–302. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Repp F, Kollmannsberger P, Roschger A, Berzlanovich A, Gruber GM, Roschger P, Wagermaier W and Weinkamer R: Coalignment of osteocyte canaliculi and collagen fibers in human osteonal bone. J Struct Biol. 199:177–186. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Liu JC, Lengner CJ, Gaur T, Lou Y, Hussain S, Jones MD, Borodic B, Colby JL, Steinman HA, van Wijnen AJ, et al: Runx2 protein expression utilizes the Runx2 P1 promoter to establish osteoprogenitor cell number for normal bone formation. J Biol Chem. 286:30057–30070. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Hoemann CD, El-Gabalawy H and McKee MD: In vitro osteogenesis assays: Influence of the primary cell source on alkaline phosphatase activity and mineralization. Pathol Biol (Paris). 57:318–323. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Li XM, Yang Q, Li XB, Cheng Q, Zhang K and Han J: Estrogen-like neuroprotection of isopsoralen against spinal cord injury through estrogen receptor ERα. Metab Brain Dis. 32:259–265. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Wang Y, Lu Y, Li Z, Zhou Y, Gu Y, Pang X, Wu J, Gobin R and Yu J: Oestrogen receptor alpha regulates the odonto/osteogenic differentiation of stem cells from apical papilla via ERK and JNK MAPK pathways. Cell Prolif. 51:e124852018. View Article : Google Scholar : PubMed/NCBI

19 

Srnec R, Divin R, Skoric M, Snasil R, Krbec M and Necas A: Use of the Peptigel with Nanofibres in the bone defects healing. Acta Chir Orthop Traumatol Cech. 85:359–365. 2018.(In Czech). PubMed/NCBI

20 

Zhang K, Wang M, Li Y, Li C, Tang S, Qu X, Feng N and Wu Y: The PERK-EIF2α-ATF4 signaling branch regulates osteoblast differentiation and proliferation by PTH. Am J Physiol Endocrinol Metab. 2019.(Epub ahead of print). View Article : Google Scholar :

21 

Xi G, Wai C, Rosen CJ and Clemmons DR: A peptide containing the receptor binding site of insulin-like growth factor binding protein-2 enhances bone mass in ovariectomized rats. Bone Res. 6:232018. View Article : Google Scholar : PubMed/NCBI

22 

Halling Linder C, Ek-Rylander B, Krumpel M, Norgård M, Narisawa S, Millán JL, Andersson G and Magnusson P: Bone alkaline phosphatase and tartrate-resistant acid phosphatase: Potential co-regulators of bone mineralization. Calcif Tissue Int. 101:92–101. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Bruderer M, Richards RG, Alini M, Stoddart MJ and Platz D: Role and regulation of runx2 in osteogenesis. Eur Cell Mater. 28:269–286. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Komori T: Runx2, an inducer of osteoblast and chondrocyte differentiation. Histochem Cell Biol. 149:313–323. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Rosen V: BMP2 signaling in bone development and repair. Cytokine Growth Factor Rev. 20:475–480. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Jang WG, Kim EJ, Kim DK, Ryoo HM, Lee KB, Kim SH, Choi HS and Koh JT: BMP2 protein regulates osteocalcin expression via Runx2- mediated Atf6 gene transcription. J Biol Chem. 287:905–915. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Stevens ML, Chaturvedi P, Rankin SA, Macdonald M, Jagannathan S, Yukawa M, Barski A and Zorn AM: Genomic integration of Wnt/β-catenin and BMP/Smad1 signaling coordinates foregut and hindgut transcriptional programs. Development. 144:1283–1295. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Zhang R, Oyajobi BO, Harris SE, Chen D, Tsao C, Deng HW and Zhao M: Wnt/β-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts. Bone. 52:145–156. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Gifre L, Vidal J, Carrasco JL, Filella X, Ruiz-Gaspà S, Muxi A, Portell E, Monegal A, Guañabens N and Peris P: Effect of recent spinal cord injury on Wnt signaling antagonists (sclerostin and Dkk-1) and their relationship with bone loss. A 12-month prospective study. J Bone Miner Res. 30:1014–1021. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Armstrong VJ, Muzylak M, Sunters A, Zaman G, Saxon LK, Price JS and Lanyon LE: Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J Biol Chem. 282:20715–20727. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Gao Y, Huang E, Zhang H, Wang J, Wu N, Chen X, Wang N, Wen S, Nan G, Deng F, et al: Crosstalk between Wnt/β-catenin and estrogen receptor signaling synergistically promotes osteogenic differentiation of mesenchymal progenitor cells. PLoS One. 8:e824362013. View Article : Google Scholar : PubMed/NCBI

32 

Bord S, Horner A, Beavan S and Compston J: Estrogen receptors alpha and beta are differentially expressed in developing human bone. J Clin Endocrinol Metab. 86:2309–2314. 2014. View Article : Google Scholar

33 

Khalid AB and Krum SA: Estrogen receptors alpha and beta in bone. Bone. 87:130–135. 2017. View Article : Google Scholar

34 

Galea GL, Meakin LB, Sugiyama T, Zebda N, Sunters A, Taipaleenmaki H, Stein GS, van Wijnen AJ, Lanyon LE and Price JS: Estrogen receptor α mediates proliferation of osteoblastic cells stimulated by estrogen and mechanical strain, but their acute down-regulation of the Wnt antagonist Sost is mediated by estrogen receptor β. J Biol Chem. 288:9035–9048. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Kondoh S, Inoue K, Igarashi K, Sugizaki H, Shirode-Fukuda Y, Inoue E, Yu T, Takeuchi JK, Kanno J, Bonewald LF and Imai Y: Estrogen receptor α in osteocytes regulates trabecular bone formation in female mice. Bone. 60:68–77. 2015. View Article : Google Scholar

36 

Windahl SH, Börjesson AE, Farman HH, Engdahl C, Movérare-Skrtic S, Sjögren K, Lagerquist MK, Kindblom JM, Koskela A, Tuukkanen J, et al: Estrogen receptor-α in osteocytes is important for trabecular bone formation in male mice. Proc Natl Acad Sci USA. 110:2294–2299. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ge L, Cui Y, Liu B, Yin X, Pang J and Han J: ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis. Mol Med Rep 19: 3469-3476, 2019.
APA
Ge, L., Cui, Y., Liu, B., Yin, X., Pang, J., & Han, J. (2019). ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis. Molecular Medicine Reports, 19, 3469-3476. https://doi.org/10.3892/mmr.2019.9999
MLA
Ge, L., Cui, Y., Liu, B., Yin, X., Pang, J., Han, J."ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis". Molecular Medicine Reports 19.5 (2019): 3469-3476.
Chicago
Ge, L., Cui, Y., Liu, B., Yin, X., Pang, J., Han, J."ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis". Molecular Medicine Reports 19, no. 5 (2019): 3469-3476. https://doi.org/10.3892/mmr.2019.9999
Copy and paste a formatted citation
x
Spandidos Publications style
Ge L, Cui Y, Liu B, Yin X, Pang J and Han J: ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis. Mol Med Rep 19: 3469-3476, 2019.
APA
Ge, L., Cui, Y., Liu, B., Yin, X., Pang, J., & Han, J. (2019). ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis. Molecular Medicine Reports, 19, 3469-3476. https://doi.org/10.3892/mmr.2019.9999
MLA
Ge, L., Cui, Y., Liu, B., Yin, X., Pang, J., Han, J."ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis". Molecular Medicine Reports 19.5 (2019): 3469-3476.
Chicago
Ge, L., Cui, Y., Liu, B., Yin, X., Pang, J., Han, J."ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis". Molecular Medicine Reports 19, no. 5 (2019): 3469-3476. https://doi.org/10.3892/mmr.2019.9999
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