Stanniocalcin 2 improved osteoblast differentiation via phosphorylation of ERK

Zhou,Juan; Li,Yinghua; Yang,Lina; Wu,Yougen; Zhou,Yunjiao; Cui,Yunqing; Yang,Gong; Hong,Yang

doi:10.3892/mmr.2016.5951

Stanniocalcin 2 improved osteoblast differentiation via phosphorylation of ERK

Authors:
- Juan Zhou
- Yinghua Li
- Lina Yang
- Yougen Wu
- Yunjiao Zhou
- Yunqing Cui
- Gong Yang
- Yang Hong
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Affiliations: Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, P.R. China
Published online on: November 16, 2016 https://doi.org/10.3892/mmr.2016.5951
Pages: 5653-5659

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Abstract

Mammalian stanniocalcin 2 (STC2) is a glycoprotein hormone with multiple functions. The present study determined the importance of STC2 in osteoblast differentiation. It was revealed that the expression of STC2 was increased during the differentiation of MC3T3-E1 cells to osteoblasts and that knockdown of STC2 reduced osteoblast differentiation and mineralization, whereas STC2 overexpression increased differentiation and mineralization. Knockdown of STC2 downregulated the expression of osteoblast-associated genes, including runt‑related transcription factor 2, collagen type I α 1 chain, osterix and osteocalcin. Overexpression of STC2 upregulated the expression of these osteoblastic genes. In addition, overexpression of STC2 enhanced the phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK1/2), whereas inhibition of ERK phosphorylation reduced osteoblast differentiation of MC3T3‑E1 cells overexpressing STC2. These findings indicated that STC2 may promote osteoblast differentiation and mineralization by regulating ERK activation.

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1	Ishibashi K, Miyamoto K, Taketani Y, Morita K, Takeda E, Sasaki S and Imai M: Molecular cloning of a second human stanniocalcin homologue (STC2). Biochem Biophys Res Commun. 250:252–258. 1998. View Article : Google Scholar : PubMed/NCBI
2	Zeiger W, Ito D, Swetlik C, Oh-hora M, Villereal ML and Thinakaran G: Stanniocalcin 2 is a negative modulator of store-operated calcium entry. Mol Cell Biol. 31:3710–3722. 2011. View Article : Google Scholar : PubMed/NCBI
3	Fang Z, Tian Z, Luo K, Song H and Yi J: Clinical significance of stanniocalcin expression in tissue and serum of gastric cancer patients. Chin J Cancer Res. 26:602–610. 2014.PubMed/NCBI
4	Arigami T, Uenosono Y, Ishigami S, Yanagita S, Hagihara T, Haraguchi N, Matsushita D, Hirahara T, Okumura H, Uchikado Y, et al: Clinical significance of stanniocalcin 2 expression as a predictor of tumor progression in gastric cancer. Oncol Rep. 30:2838–2844. 2013.PubMed/NCBI
5	Yokobori T, Mimori K, Ishii H, Iwatsuki M, Tanaka F, Kamohara Y, Ieta K, Kita Y, Doki Y, Kuwano H and Mori M: Clinical significance of stanniocalcin 2 as a prognostic marker in gastric cancer. Ann Surg Oncol. 17:2601–2607. 2010. View Article : Google Scholar : PubMed/NCBI
6	Wang YY, Li L, Zhao ZS and Wang HJ: Clinical utility of measuring expression levels of KAP1, TIMP1 and STC2 in peripheral blood of patients with gastric cancer. World J Surg Oncol. 11:812013. View Article : Google Scholar : PubMed/NCBI
7	Volland S, Kugler W, Schweigerer L, Wilting J and Becker J: Stanniocalcin 2 promotes invasion and is associated with metastatic stages in neuroblastoma. Int J Cancer. 125:2049–2057. 2009. View Article : Google Scholar : PubMed/NCBI
8	Zhou H, Li YY, Zhang WQ, Lin D, Zhang WM and Dong WD: Expression of stanniocalcin-1 and stanniocalcin-2 in laryngeal squamous cell carcinoma and correlations with clinical and pathological parameters. PLoS One. 9:e954662014. View Article : Google Scholar : PubMed/NCBI
9	Kita Y, Mimori K, Iwatsuki M, Yokobori T, Ieta K, Tanaka F, Ishii H, Okumura H, Natsugoe S and Mori M: STC2: A predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma. Ann Surg Oncol. 18:261–272. 2011. View Article : Google Scholar : PubMed/NCBI
10	Hou J, Wang Z, Xu H, Yang L, Yu X, Yang Z, Deng Y, Meng J, Feng Y, Guo X and Yang G: Stanniocalicin 2 suppresses breast cancer cell migration and invasion via the PKC/claudin-1-mediated signaling. PLoS One. 10:e01221792015. View Article : Google Scholar : PubMed/NCBI
11	Chang AC, Hook J, Lemckert FA, McDonald MM, Nguyen MA, Hardeman EC, Little DG, Gunning PW and Reddel RR: The murine stanniocalcin 2 gene is a negative regulator of postnatal growth. Endocrinology. 149:2403–2410. 2008. View Article : Google Scholar : PubMed/NCBI
12	Gagliardi AD, Kuo EY, Raulic S, Wagner GF and DiMattia GE: Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs. Am J Physiol Endocrinol Metab. 288:E92–E105. 2005. View Article : Google Scholar : PubMed/NCBI
13	Rimbault M, Beale HC, Schoenebeck JJ, Hoopes BC, Allen JJ, Kilroy-Glynn P, Wayne RK, Sutter NB and Ostrander EA: Derived variants at six genes explain nearly half of size reduction in dog breeds. Genome Res. 23:1985–1995. 2013. View Article : Google Scholar : PubMed/NCBI
14	Raulic S, Ramos-Valdes Y and DiMattia GE: Stanniocalcin 2 expression is regulated by hormone signalling and negatively affects breast cancer cell viability in vitro. J Endocrinol. 197:517–529. 2008. View Article : Google Scholar : PubMed/NCBI
15	Takei Y, Yamamoto H, Masuda M, Sato T, Taketani Y and Takeda E: Stanniocalcin 2 is positively and negatively controlled by 1,25(OH)(2)D(3) and PTH in renal proximal tubular cells. J Mol Endocrinol. 42:261–268. 2009. View Article : Google Scholar : PubMed/NCBI
16	Zhang W and Aletta JM: EGF-mediated phosphorylation of extracellular signal-regulated kinases in osteoblastic cells. J Cell Physiol. 162:348–358. 1995. View Article : Google Scholar : PubMed/NCBI
17	Chaudhary LR and Avioli LV: Activation of extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2) by FGF-2 and PDGF-BB in normal human osteoblastic and bone marrow stromal cells: Differences in mobility and in-gel renaturation of ERK1 in human, rat, and mouse osteoblastic cells. Biochem Biophys Res Commun. 238:134–139. 1997. View Article : Google Scholar : PubMed/NCBI
18	Lai CF, Chaudhary L, Fausto A, Halstead LR, Ory DS, Avioli LV and Cheng SL: Erk is essential for growth, differentiation, integrin expression and cell function in human osteoblastic cells. J Biol Chem. 276:14443–14450. 2001.PubMed/NCBI
19	Xiao G, Gopalakrishnan R, Jiang D, Reith E, Benson MD and Franceschi RT: Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. J Bone Miner Res. 17:101–110. 2002. View Article : Google Scholar : PubMed/NCBI
20	Shim JH, Greenblatt MB, Zou W, Huang Z, Wein MN, Brady N, Hu D, Charron J, Brodkin HR, Petsko GA, et al: Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts. J Clin Invest. 123:4010–4022. 2013. View Article : Google Scholar : PubMed/NCBI
21	Zhao KW, Murray EJ and Murray SS: Spp24 derivatives stimulate a Gi-protein coupled receptor-Erk1/2 signaling pathway and modulate gene expressions in W-20-17 cells. J Cell Biochem. 116:767–777. 2015. View Article : Google Scholar : PubMed/NCBI
22	Twigg SR, Vorgia E, McGowan SJ, Peraki I, Fenwick AL, Sharma VP, Allegra M, Zaragkoulias A, Akha E Sadighi, Knight SJ, et al: Reduced dosage of ERF causes complex craniosynostosis in humans and mice and links ERK1/2 signaling to regulation of osteogenesis. Nat Genet. 45:308–313. 2013. View Article : Google Scholar : PubMed/NCBI
23	Quarto N, Senarath-Yapa K, Renda A and Longaker MT: TWIST1 silencing enhances in vitro and in vivo osteogenic differentiation of human adipose-derived stem cells by triggering activation of BMP-ERK/FGF signaling and TAZ upregulation. Stem Cells. 33:833–847. 2015. View Article : Google Scholar : PubMed/NCBI
24	Tamma R, Sun L, Cuscito C, Lu P, Corcelli M, Li J, Colaianni G, Moonga SS, Di Benedetto A, Grano M, et al: Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia. Proc Natl Acad Sci USA. 110:18644–18649. 2013. View Article : Google Scholar : PubMed/NCBI
25	Wang H, Wu K, Sun Y, Li Y, Wu M, Qiao Q, Wei Y, Han ZG and Cai B: STC2 is upregulated in hepatocellular carcinoma and promotes cell proliferation and migration in vitro. BMB Rep. 45:629–634. 2012. View Article : Google Scholar : PubMed/NCBI
26	Yaffe D and Saxel O: Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature. 270:725–727. 1977. View Article : Google Scholar : PubMed/NCBI
27	Huang YF, Lin JJ, Lin CH, Su Y and Hung SC: c-Jun N-terminal kinase 1 negatively regulates osteoblastic differentiation induced by BMP2 via phosphorylation of Runx2 at Ser104. J Bone Miner Res. 27:1093–1105. 2012. View Article : Google Scholar : PubMed/NCBI
28	Zhong Z, Zylstra-Diegel CR, Schumacher CA, Baker JJ, Carpenter AC, Rao S, Yao W, Guan M, Helms JA, Lane NE, et al: Wntless functions in mature osteoblasts to regulate bone mass. Proc Natl Acad Sci USA. 109:E2197–E2204. 2012. View Article : Google Scholar : PubMed/NCBI
29	Wang X, Harimoto K, Liu J, Guo J, Hinshaw S, Chang Z and Wang Z: Spata4 promotes osteoblast differentiation through Erk-activated Runx2 pathway. J Bone Miner Res. 26:1964–1973. 2011. View Article : Google Scholar : PubMed/NCBI
30	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
31	Stasko SE and Wagner GF: Possible roles for stanniocalcin during early skeletal patterning and joint formation in the mouse. J Endocrinol:. 171:237–248. 2001. View Article : Google Scholar : PubMed/NCBI