Skip to main content
SpringerLink
Log in

The role of oncostatin M regulates osteoblastic differentiation of dental pulp stem cells through STAT3 pathway

  • Original Article
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells, which have the self-renewal and multi-lineage differentiation potential, including chondrocytes, adipocytes, neural cells and osteoblasts. So they play a significant role in pulp repair and bone regeneration. Oncostatin M (OSM), one of the IL-6 family cytokines, inhibits adipogenic differentiation and stimulates osteogenic differentiation of human bone marrow mesenchymal stem cells. However, the effect of OSM on DPSCs is unclear. We found that OSM induced osteogenic differentiation of DPSCs, promoting matrix mineralization as measured by Alizarin Red S staining. OSM also increased expression of osteogenesis-associated gene products Alkaline phosphatase, Bone morphogenetic protein 2 (BMP2), Runt-related transcription factor 2 and Osteocalcin (OCN) as assessed by immunoblotting. We also found that OSM activated the Signal Transducer And Activator Of Transcription 3 (STAT3) pathway during the osteogenic differentiation of DPSCs. Blocking the osteogenic differentiation by silencing of STAT3 can significantly inhibit OSM-induced osteogenic differentiation of DPSCs and the expression of related genes, furthermore matrix mineralization was also suppressed. In summary, OSM promotes osteoblastic differentiation of DPSCs and osteogenesis-related genes expression through the JAK3/STAT3 signaling pathway which may be useful for the autologous transplantation of DPSCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

DPSCs:

Dental pulp stem cells

MSCs:

Mesenchymal stem cells

OSM:

Oncostatin M

STAT3:

Signal transducer and activator of transcription 3

ALP:

Alkaline phosphatase

BMP2:

Bone morphogenetic protein 2

Runx2:

Runt-related transcription factor 2

OC:

Osteogenic differentiation

JAK3:

Janus kinase 3

hADSCs:

Human adipose mesenchymal stem cells

OCN:

Osteocalcin

siJAK3:

JAK3 siRNA

siSTAT3:

STAT3 siRNA

OSMR:

Oncostatin M receptor

References

  • Alge DL, Zhou D, Adams LL, Wyss BK, Shadday MD, Woods EJ, Chu TG, Goebel WS (2010) Donormatched comparison of dental pulp stem cells and bone marrow-derived mesenchymal stem cells in a rat model. J Tissue Eng Regen Med 4:73

    CAS  Google Scholar 

  • Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S (2008) Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues. Stem Cells 26:1787–1795

    Article  CAS  Google Scholar 

  • Bellido T, O’Brien CA, Roberson PK, Manolagas SC (1998) Transcriptional activation of the p21 waf1, cip1, sdi1 gene by interleukin-6 type cytokines a prerequisite for their pro-differentiating and anti-apoptotic effects on human osteoblastic cells. J Biol Chem 273:21137–21144

    Article  CAS  Google Scholar 

  • Bernard C, Merval R, Lebret M, Delerive P, Dusanter-Fourt I, Lehoux S, Creminon C, Staels B, Maclouf J, Tedgui A (1999) Oncostatin m induces interleukin-6 and cyclooxygenase-2 expression in human vascular smooth muscle cells synergy with interleukin-1β. Circ Res 85:1124–1131

    Article  CAS  Google Scholar 

  • Chipoy C, Berreur M, Couillaud S, Pradal G, Vallette F, Colombeix C, Redini F, Heymann D, Blanchard F (2004) Downregulation of osteoblast markers and induction of the glial fibrillary acidic protein by oncostatin m in osteosarcoma cells require pkcδ and stat3. J Bone Miner Res 19:1850–1861

    Article  CAS  Google Scholar 

  • Demyanets S, Kaun C, Rychli K, Pfaffenberger S, Kastl SP, Hohensinner PJ, Rega G, Katsaros KM, Afonyushkin T, Bochkov VN, Paireder M, Huk I, Maurer G, Huber K, Wojta J (2011) Oncostatin M-enhanced vascular endothelial growth factor expression in human vascular smooth muscle cells involves pi3 k-, p38 mapk-, erk1/2-and stat1/stat3-dependent pathways and is attenuated by interferon-γ. Basic Res Cardiol 106:217–231

    Article  CAS  Google Scholar 

  • Gadient RA, Patterson PH (1999) Leukemia inhibitory factor, interleukin 6, and other cytokines using the gp130 transducing receptor: roles in inflammation and injury. Stem Cells 17:127–137

    Article  CAS  Google Scholar 

  • Gomez-Lechon M (1999) Oncostatin m: signal transduction and biological activity. Life Sci 65:2019–2030

    Article  CAS  Google Scholar 

  • Grant SL, Begley CG (1999) The oncostatin m signalling pathway: reversing the neoplastic phenotype? Mol Med Today 5:406–412

    Article  CAS  Google Scholar 

  • Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (dpscs) in vitro and in vivo. Proc Natl Acad Sci 97:13625–13630

    Article  CAS  Google Scholar 

  • Gronthos S, Brahim J, Li W, Fisher L, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S (2002) Stem cell properties of human dental pulp stem cells. J Dent Res 81:531–535

    Article  CAS  Google Scholar 

  • Guihard P, Danger Y, Brounais B, David E, Brion R, Delecrin J, Richards CD, Chevalier S, Rédini F, Heymann D, Gascan H, Blanchard F (2012) Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling. Stem Cells 30:762–772

    Article  CAS  Google Scholar 

  • Guihard P, Boutet MA, Brounais-Le Royer B, Gamblin AL, Amiaud J, Renaud A, Berreur M, Rédini F, Heymann D, Layrolle P, Blanchard F (2015) Oncostatin m, an inflammatory cytokine produced by macrophages, supports intramembranous bone healing in a mouse model of tibia injury. Am J Pathol 185:765–775

    Article  CAS  Google Scholar 

  • Heymann D, Rousselle AV (2000) gp130 cytokine family and bone cells. Cytokine 12:1455–1468

    Article  CAS  Google Scholar 

  • Hoermann G, Cerny-Reiterer S, Perné A, Klauser M, Hoetzenecker K, Klein K, Müllauer L, Gröger M, Nijman SM, Klepetko W, Valent P, Mayerhofer M (2011) Identification of oncostatin M as a STAT5-dependent mediator of bone marrow remodeling in KIT D816V-positive systemic mastocytosis. Am J Pathol 178:2344–2356

    Article  CAS  Google Scholar 

  • Homayounfar N, Verma P, Nosrat A, El Ayachi I, Yu Z, Romberg E, Huang GT, Fouad AF (2016) Isolation, characterization, and differentiation of dental pulp stem cells in ferrets. J Endod 42:418–424

    Article  Google Scholar 

  • Huang GJ, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88:792–806

    Article  CAS  Google Scholar 

  • Jay PR, Centrella M, Lorenzo J, Bruce A, Horowitz MC (1996) Oncostatin-m: a new bone active cytokine that activates osteoblasts and inhibits bone resorption. Endocrinology 137:1151–1158

    CAS  Google Scholar 

  • Lee YM, Shin SY, Jue SS, Kwon IK, Cho EH, Cho ES, Park SH, Kim EC (2013) The role of pin1 on odontogenic and adipogenic differentiation in human dental pulp stem cells. Stem Cells Dev 23:618–630

    Article  Google Scholar 

  • Li J (2013) Jak-stat and bone metabolism. JAK-STAT 2:e23930

    Google Scholar 

  • Malaval L, Liu F, Vernallis AB, Aubin JE (2005) Gp130/osmr is the only lif/il-6 family receptor complex to promote osteoblast differentiation of calvaria progenitors. J Cell Physiol 204:585–593

    Article  CAS  Google Scholar 

  • Malik N, Haugen HS, Modrell B, Shoyab M, Clegg CH (1995) Developmental abnormalities in mice transgenic for bovine oncostatin m. Mol Cell Biol 15:2349–2358

    Article  CAS  Google Scholar 

  • Miyaoka Y, Tanaka M, Naiki T, Miyajima A (2006) Oncostatin m inhibits adipogenesis through the ras/erk and stat5 signaling pathways. J Biol Chem 281:37913–37920

    Article  CAS  Google Scholar 

  • Nagata T, Kai H, Shibata R, Koga M, Yoshimura A, Imaizumi T (2003) Oncostatin m, an interleukin-6 family cytokine, upregulates matrix metalloproteinase-9 through the mitogen-activated protein kinase kinase-extracellular signal-regulated kinase pathway in cultured smooth muscle cells. Arterioscler Thromb Vasc Biol 23:588–593

    Article  CAS  Google Scholar 

  • Nakatsuka R, Nozaki T, Uemura Y, Matsuoka Y, Sasaki Y, Shinohara M, Ohura K, Sonoda Y (2010) 5-aza-2-deoxycytidine treatment induces skeletal myogenic differentiation of mouse dental pulp stem cells. Arch Oral Biol 55:350–357

    Article  CAS  Google Scholar 

  • Pelletier JP, Martel-Pelletier J (2003) Oncostatin m: foe or friend? Arthritis Rheum 48:3301–3303

    Article  Google Scholar 

  • Pflanz S, Hibbert L, Mattson J, Rosales R, Vaisberg E, Bazan JF, Phillips JH, McClanahan TK, de Waal Malefyt R, Kastelein RA (2004) Wsx-1 and glycoprotein 130 constitute a signal-transducing receptor for il-27. J Immunol 172:2225–2231

    Article  CAS  Google Scholar 

  • Rodríguez-Lozano FJ, Insausti CL, Iniesta F, Blanquer M, Ramírez MD, Meseguer L, Meseguer-Henarejos AB, Marín N, Martínez S, Moraleda JM (2012) Mesenchymal dental stem cells in regenerative dentistry. Med OralPatol Oral Cir Bucal 17:e1062

    Article  Google Scholar 

  • Shioi A, Katagi M, Okuno Y, Mori K, Jono S, Koyama H, Nishizawa Y (2002) Induction of bone-type alkaline Phosphatase in human vascular smooth muscle cells roles of tumor necrosis factor-α and oncostatin M derived from macrophages. Circ Res 91:9–16

    Article  CAS  Google Scholar 

  • Smyth DC, Takenaka S, Yeung C, Richards CD (2015) Oncostatin M regulates osteogenic differentiation of murine adipose-derived mesenchymal progenitor cells through a PKCdelta-dependent mechanism. Cell Tissue Res 360:309–319

    Article  CAS  Google Scholar 

  • Song HY, Jeon ES, Kim JI, Jung JS, Kim JH (2007) Oncostatin m promotes osteogenesis and suppresses adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells. J Cell Biochem 101:1238–1251

    Article  CAS  Google Scholar 

  • Taguchi Y, Yamamoto M, Yamate T, Lin SC, Mocharla H, DeTogni P, Nakayama N, Boyce B, Abe E, Manolagas S (1998) Interleukin-6-type cytokines stimulate mesenchymal progenitor differentiation toward the osteoblastic lineage. Proc Assoc Am Phys 110:559–574

    CAS  Google Scholar 

  • Tanaka M, Miyahima A (2003) Onconstatin m, a multifunctional cytokine. Rev Physiol Biochem Pharmacol 149:39–52

    CAS  Google Scholar 

  • Walker EC, McGregor NE, Poulton IJ, Solano M, Pompolo S, Fernandes TJ, Constable MJ, Nicholson GC, Zhang JG, Nicola NA, Gillespie MT, Martin TJ, Sims NA (2010) Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice. J Clin Invest 120:582–592

  • Yanai N, Obinata M (2001) Oncostatin m regulates mesenchymal cell differentiation and enhances hematopoietic supportive activity of bone marrow stromal cell lines. In Vitro Cell Dev Biol-Anim 37:698–704

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work is supported by National Natural Science Foundation of China under Grant 81500809 and Funding of Jiangsu Innovation Program for Graduate Education KYZZ15-0091, the Fundamental Research Funds for the Central Universities; the Graduate Student Innovation of Science and Technology Projects in Jiangsu Province (Grant no. SJLX0588); the “Top Six Types of Talents” Financial Assistance of Jiangsu Province Grant (No. 10).

Author information

Author notes

    Authors and Affiliations

    1. Department of Stomatology, Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226000, China

      Xingmei Feng, Shuling Shen, Peipei Cao, Ye Zhang, Ke Zheng & Guijuan Feng

    2. Department of Mathematics, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, China

      Linhe Zhu

    3. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226000, China

      Dongmei Zhang

    Authors
    1. Xingmei Feng
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Shuling Shen
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Peipei Cao
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Linhe Zhu
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Ye Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Ke Zheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Guijuan Feng
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Dongmei Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Guijuan Feng or Dongmei Zhang.

    Additional information

    Xingmei Feng and Shuling Shen contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Feng, X., Shen, S., Cao, P. et al. The role of oncostatin M regulates osteoblastic differentiation of dental pulp stem cells through STAT3 pathway. Cytotechnology 68, 2699–2709 (2016). https://doi.org/10.1007/s10616-016-9995-9

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10616-016-9995-9

    Keywords

    Search

    Navigation