Estradiol‑enhanced osteogenesis of rat bone marrow stromal cells is associated with the JNK pathway

Song,Nan; Wang,Zhi‑Min; He,Li‑Juan; Xu,Yan; Ren,Yan‑Ling

doi:10.3892/mmr.2017.7699

Estradiol‑enhanced osteogenesis of rat bone marrow stromal cells is associated with the JNK pathway

Authors:
- Nan Song
- Zhi‑Min Wang
- Li‑Juan He
- Yan Xu
- Yan‑Ling Ren
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Affiliations: Key Laboratory of Ministry of Education for TCM Viscera‑State Theory and Applications, Ministry of Education of China, Shenyang, Liaoning 110847, P.R. China, The Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China, School of Chinese Medical Formulae, College of Basic Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China, College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China
Published online on: October 3, 2017 https://doi.org/10.3892/mmr.2017.7699
Pages: 8589-8594
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bone marrow stromal cells (BMSCs) can differentiate into osteoblasts. The present study investigated the osteogenic effects of estradiol, as well as the role of the c‑Jun N‑terminal kinase (JNK) signaling pathway in promoting estradiol‑enhanced osteogenesis of rat (r)BMSCs. rBMSCs were treated for 7 days with or without estradiol and further treated with or without the JNK‑specific inhibitor SP600125. The role of estrogen during rBMSC osteogenesis was evaluated by alkaline phosphatase activity and mineralized nodule formation using the Gomori method and Alizarin red S staining, respectively. Subsequently, the mRNA expression levels of transforming growth factor-β1 (TGF‑β1) and core‑binding factor α1 (Cbfα1) were evaluated by reverse transcription‑quantitative polymerase chain reaction, and TGF‑β1, Cbfα1 and phosphorylated (p)‑JNK protein expression was detected by western blotting. All groups treated with SP600125 expressed low levels of TGF‑β1 and Cbfα1 mRNA and protein, and low p‑JNK protein expression. Compared with the control cells, rBMSCs cultured with estradiol exhibited a significant upregulation in the expression levels of osteogenic genes and proteins. The present study demonstrated that estradiol enhanced osteogenic differentiation of rBMSCs and that the JNK signaling pathway was involved in this process, providing insights into the molecular mechanisms involved in rBMSC osteogenesis upon estradiol stimulation.

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1	Siris ES, Miller PD, Barrett-Connor E, Faulkner KG, Wehren LE, Abbott TA, Berger ML, Santora AC and Sherwood LM: Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: Results from the National Osteoporosis Risk Assessment. JAMA. 286:2815–2822. 2001. View Article : Google Scholar : PubMed/NCBI
2	Rachner TD, Khosla S and Hofbauer LC: Osteoporosis: Now and the future. Lancet. 377:1276–1287. 2011. View Article : Google Scholar : PubMed/NCBI
3	Al-Rahbi B, Zakaria R, Othman Z, Hassan A and Ahmad AH: Enhancement of BDNF concentration and restoration of the hypothalamic-pituitary-adrenal axis accompany reduced depressive-like behaviour in stressed ovariectomised rats treated with either Tualang honey or estrogen. ScientificWorldJournal. 2014:3108212014. View Article : Google Scholar : PubMed/NCBI
4	Chen FP, Hu CH and Wang KC: Estrogen modulates osteogenic activity and estrogen receptor mRNA in mesenchymal stem cells of women. Climacteric. 16:154–160. 2013. View Article : Google Scholar : PubMed/NCBI
5	Prockop DJ: Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 276:71–74. 1997. View Article : Google Scholar : PubMed/NCBI
6	Tan SL, Ahmad TS, Selvaratnam L and Kamarul T: Isolation, characterization and the multi-lineage differentiation potential of rabbit bone marrow-derived mesenchymal stem cells. J Anat. 222:437–450. 2013. View Article : Google Scholar : PubMed/NCBI
7	Chen M, Feng W, Cao H, Zou L, Chen C, Baatrup A, Nielsen AB, Li H, Kassem M, Zou X and Bünger C: A traditional Chinese medicine formula extracts stimulate proliferation and inhibit mineralization of human mesenchymal stem cells in vitro. J Ethnopharmacol. 125:75–82. 2009. View Article : Google Scholar : PubMed/NCBI
8	Zhou DA, Zheng HX, Wang CW, Shi D and Li JJ: Influence of glucocorticoids on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. BMC Musculoskelet Disord. 15:2392014. View Article : Google Scholar : PubMed/NCBI
9	Cargnello M and Roux PP: Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 75:50–83. 2011. View Article : Google Scholar : PubMed/NCBI
10	Kim HK, Kim MG and Leem KH: Osteogenic activity of collagen peptide via ERK/MAPK pathway mediated boosting of collagen synthesis and its therapeutic efficacy in osteoporotic bone by back-scattered electron imaging and microarchitecture analysis. Molecules. 18:15474–15489. 2013. View Article : Google Scholar : PubMed/NCBI
11	Sonowal H, Kumar A, Bhattacharyya J, Gogoi PK and Jaganathan BG: Inhibition of actin polymerization decreases osteogeneic differentiation of mesenchymal stem cells through p38 MAPK pathway. J Biomed Sci. 20:712013. View Article : Google Scholar : PubMed/NCBI
12	Kwon HS, Johnson TV and Tomarev SI: Myocilin stimulates osteogenic differentiation of mesenchymal stem cells through mitogen-activated protein kinase signaling. J Biol Chem. 288:16882–16894. 2013. View Article : Google Scholar : PubMed/NCBI
13	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
14	Marom R, Shur I, Solomon R and Benayahu D: Characterization of adhesion and differentiation markers of osteogenic marrow stromal cells. J Cell Physiol. 202:41–48. 2005. View Article : Google Scholar : PubMed/NCBI
15	Li XD, Wang JS, Chang B, Chen B, Guo C, Hou GQ, Huang DY and Du SX: Panax notoginseng saponins promotes proliferation and osteogenic differentiation of rat bone marrow stromal cells. J Ethnopharmacol. 134:268–274. 2011. View Article : Google Scholar : PubMed/NCBI
16	Komori T: Animal models for osteoporosis. Eur J Pharmacol. 759:287–294. 2015. View Article : Google Scholar : PubMed/NCBI
17	Guicheux J, Lemonnier J, Ghayor C, Suzuki A, Palmer G and Caverzasio J: Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation. J Bone Miner Res. 18:2060–2068. 2003. View Article : Google Scholar : PubMed/NCBI
18	Byers BA, Pavlath GK, Murphy TJ, Karsenty G and Garcia AJ: Cell-type-dependent up-regulation of in vitro mineralization after overexpression of the osteoblast-specific transcription factor Runx2/Cbfal. J Bone Miner Res. 17:1931–1944. 2002. View Article : Google Scholar : PubMed/NCBI
19	Teplyuk NM, Haupt LM, Ling L, Dombrowski C, Mun FK, Nathan SS, Lian JB, Stein JL, Stein GS, Cool SM and van Wijnen AJ: The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts. J Cell Biochem. 107:144–154. 2009. View Article : Google Scholar : PubMed/NCBI
20	Ngueguim FT, Khan MP, Donfack JH, Siddiqui JA, Tewari D, Nagar GK, Tiwari SC, Theophile D, Maurya R and Chattopadhyay N: Evaluation of cameroonian plants towards experimental bone regeneration. J Ethnopharmacol. 141:331–337. 2012. View Article : Google Scholar : PubMed/NCBI