Advertisement

Calcified Tissue International

, Volume 104, Issue 2, pp 201–206 | Cite as

Nephronectin Expression is Inhibited by Inorganic Phosphate in Osteoblasts

  • Tadashi Kato
  • Atsushi YamadaEmail author
  • Kiyohito Sasa
  • Kentaro Yoshimura
  • Naoko Morimura
  • Hiroaki Ogata
  • Akiko Sakashita
  • Ryutaro Kamijo
Original Research
  • 49 Downloads

Abstract

Nephronectin (Npnt), an extracellular matrix protein, is known to be a ligand of integrin α8β1, and it has also been known to play critical roles as various organs. In the present study, elevated extracellular inorganic phosphate (Pi) strongly inhibited the expression of Npnt in MC3T3-E1 cells, while the existence of extracellular calcium (Ca) was indispensable for its effect. Furthermore, Pi-induced inhibition of Npnt gene expression was recovered by inhibitors of both sodium-dependent Pi transporter (Pit) and fibroblast growth factor receptors (Fgfrs). These results demonstrated that Npnt gene expression is regulated by extracellular Pi via Pit and Fgfrs.

Keywords

Nephronectin Phosphate Calcium MC3T3-E1 FGFR 

Notes

Acknowledgements

This work was supported in part by the Project to Establish Strategic Research Center for Innovative Dentistry by the Ministry of Education, Culture, Sports, Science and Technology of Japan (S1411009), the Private University Research Branding Project from MEXT of Japan, and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (16K15782, 15H05016, 15K11051, 17K09737).

Author Contributions

TK, AY, KS, KY, NM, HO, AS, and RK involved in study concept. AY, KS, and RK: involved in formal analysis; AY, HO, AS, and RK acquired funding; TK investigated the study; TK, AY, and RK applied methodology for the study; AY and RK administrated the project; HO, AS, and RK collected the resources; AY and RK supervised and validated the study; TK and AY wrote the original manuscript; TK, AY, and RK reviewed and edited the original manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest in regard to this study.

Human and Animal Rights and Informed Consent

All animal experiments were performed in accordance with the guide for care and use of laboratory animals and approved by the Showa University Animal Care Use and Committee.

Supplementary material

223_2018_484_MOESM1_ESM.tif (48 kb)
Supplementary material 1 (TIF 48 KB)
223_2018_484_MOESM2_ESM.tif (45 kb)
Supplementary material 2 (TIF 44 KB)

References

  1. 1.
    Morimura N, Tezuka Y, Watanabe N, Yasuda M, Miyatani S, Hozumi N, Tezuka Ki K (2001) Molecular cloning of POEM: a novel adhesion molecule that interacts with alpha8beta1 integrin. J Biol Chem 276:42172–42181CrossRefGoogle Scholar
  2. 2.
    Kahai S, Lee SC, Seth A, Yang BB (2010) Nephronectin promotes osteoblast differentiation via the epidermal growth factor-like repeats. FEBS Lett 584:233–238CrossRefGoogle Scholar
  3. 3.
    Brandenberger R, Schmidt A, Linton J, Wang D, Backus C, Denda S, Müller U, Reichardt LF (2001) Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney. J Cell Biol 154:447–458CrossRefGoogle Scholar
  4. 4.
    Linton JM, Martin GR, Reichardt LF (2007) The ECM protein nephronectin promotes kidney development via integrin alpha8beta1-mediated stimulation of Gdnf expression. Development 134:2501–2509CrossRefGoogle Scholar
  5. 5.
    Miyazono A, Yamada A, Morimura N, Takami M, Suzuki D, Kobayashi M, Tezuka K, Yamamoto M, Kamijo R (2007) TGF-beta suppresses POEM expression through ERK1/2 and JNK in osteoblasts. FEBS Lett 581:5321–5326CrossRefGoogle Scholar
  6. 6.
    Tsukasaki M, Yamada A, Suzuki D, Aizawa R, Miyazono A, Miyamoto Y, Suzawa T, Takami M, Yoshimura K, Morimura N, Yamamoto M, Kamijo R (2011) Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-alpha. Biochem Biophys Res Commun 410:766–770CrossRefGoogle Scholar
  7. 7.
    Kurosawa T, Yamada A, Takami M, Suzuki D, Saito Y, Hiranuma K, Enomoto T, Morimura N, Yamamoto M, Iijima T, Shirota T, Itabe H, Kamijo R (2015) Expression of nephronectin is inhibited by oncostatin M via both JAK/STAT and MAPK pathways. FEBS Open Bio 5:303–307CrossRefGoogle Scholar
  8. 8.
    Iezumi Y, Yamada A, Minami E, Ikehata M, Yoshida Y, Kato T, Morimura N, Ogata H, Sakashita A, Iijima T, Chikazu D, Kamijo R (2017) IL-1beta suppresses nephronectin expression in osteoblasts via ERK1/2 and JNK. Biochem Biophys Res Commun 493:773–775CrossRefGoogle Scholar
  9. 9.
    Michigami T (2013) Extracellular phosphate as a signaling molecule. Contrib Nephrol 180:14–24CrossRefGoogle Scholar
  10. 10.
    Beck GR Jr, Moran E, Knecht N (2003) Inorganic phosphate regulates multiple genes during osteoblast differentiation, including Nrf2. Exp Cell Res 288:288–300CrossRefGoogle Scholar
  11. 11.
    Kimata M, Michigami T, Tachikawa K, Okada T, Koshimizu T, Yamazaki M, Kogo M, Ozono K (2010) Signaling of extracellular inorganic phosphate up-regulates cyclin D1 expression in proliferating chondrocytes via the Na+/Pi cotransporter Pit-1 and Raf/MEK/ERK pathway. Bone 47:938–947CrossRefGoogle Scholar
  12. 12.
    Nishino J, Yamazaki M, Kawai M, Tachikawa K, Yamamoto K, Miyagawa K, Kogo M, Ozono K, Michigami T (2017) Extracellular phosphate induces the expression of dentin matrix protein 1 through the FGF receptor in osteoblasts. J Cell Biochem 118:1151–1163CrossRefGoogle Scholar
  13. 13.
    Bergwitz C, Juppner H (2011) Phosphate sensing. Adv Chronic Kidney Dis 18:132–144CrossRefGoogle Scholar
  14. 14.
    Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK (2001) Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 12:2131–2138Google Scholar
  15. 15.
    Kalantar-Zadeh K, Kuwae N, Regidor DL, Kovesdy CP, Kilpatrick RD, Shinaberger CS, McAllister CJ, Budoff MJ, Salusky IB, Kopple JD (2006) Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 70:771–780CrossRefGoogle Scholar
  16. 16.
    Katsumata K, Kusano K, Hirata M, Tsunemi K, Nagano N, Burke SK, Fukushima N (2003) Sevelamer hydrochloride prevents ectopic calcification and renal osteodystrophy in chronic renal failure rats. Kidney Int 64:441–450CrossRefGoogle Scholar
  17. 17.
    Arai-Nunota N, Mizobuchi M, Ogata H, Yamazaki-Nakazawa A, Kumata C, Kondo F, Hosaka N, Koiwa F, Kinugasa E, Shibata T, Akizawa T (2014) Intravenous phosphate loading increases fibroblast growth factor 23 in uremic rats. PLoS ONE 9:e91096CrossRefGoogle Scholar
  18. 18.
    Wolf M (2010) Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol 21:1427–1435CrossRefGoogle Scholar
  19. 19.
    Hiranuma K, Yamada A, Kurosawa T, Aizawa R, Suzuki D, Saito Y, Nagahama R, Ikehata M, Tsukasaki M, Morimura N, Chikazu D, Maki K, Shirota T, Takami M, Yamamoto M, Iijima T, Kamijo R (2016) Expression of nephronectin is enhanced by 1alpha,25-dihydroxyvitamin D3. FEBS Open Bio 6:914–918CrossRefGoogle Scholar
  20. 20.
    Kato T, Yamada A, Ikehata M, Yoshida Y, Sasa K, Morimura N, Sakashita A, Iijima T, Chikazu D, Ogata H, Kamijo R (2018) FGF-2 suppresses expression of nephronectin via JNK and PI3K pathways. FEBS Open Bio 8:836–842CrossRefGoogle Scholar
  21. 21.
    Jung YK, Han MS, Park HR, Lee EJ, Jang JA, Kim GW, Lee SY, Moon D, Han S (2018) Calcium-phosphate complex increased during subchondral bone remodeling affects earlystage osteoarthritis. Sci Rep 8:487CrossRefGoogle Scholar
  22. 22.
    Collins JF, Bai L, Ghishan FK (2004) The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors. Pflugers Arch 447:647–652CrossRefGoogle Scholar
  23. 23.
    Loghman-Adham M (1996) Use of phosphonocarboxylic acids as inhibitors of sodium-phosphate cotransport. Gen Pharmacol 27:305–312CrossRefGoogle Scholar
  24. 24.
    Foster BL, Nociti FH Jr, Swanson EC, Matsa-Dunn D, Berry JE, Cupp CJ, Zhang P, Somerman MJ (2006) Regulation of cementoblast gene expression by inorganic phosphate in vitro. Calcif Tissue Int 78:103–112CrossRefGoogle Scholar
  25. 25.
    Sugita A, Kawai S, Hayashibara T, Amano A, Ooshima T, Michigami T, Yoshikawa H, Yoneda T (2011) Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis. J Biol Chem 286:3094–3103CrossRefGoogle Scholar
  26. 26.
    Durcan L, Bolster F, Kavanagh EC, McCarthy GM (2014) The structural consequences of calcium crystal deposition. Rheum Dis Clin North Am 40:311–328CrossRefGoogle Scholar
  27. 27.
    Nasi S, So A, Combes C, Daudon M, Busso N (2016) Interleukin-6 and chondrocyte mineralisation act in tandem to promote experimental osteoarthritis. Ann Rheum Dis 75:1372–1379CrossRefGoogle Scholar
  28. 28.
    Kawai M, Kinoshita S, Ozono K, Michigami T (2016) Inorganic phosphate activates the AKT/mTORC1 pathway and shortens the life span of an alphaKlotho-deficient model. J Am Soc Nephrol 27:2810–2824Google Scholar
  29. 29.
    Okamoto T, Taguchi M, Osaki T, Fukumoto S, Fujita T (2014) Phosphate enhances reactive oxygen species production and suppresses osteoblastic differentiation. J Bone Miner Metab 32:393–399CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tadashi Kato
    • 1
    • 2
  • Atsushi Yamada
    • 1
    Email author
  • Kiyohito Sasa
    • 1
  • Kentaro Yoshimura
    • 1
  • Naoko Morimura
    • 3
  • Hiroaki Ogata
    • 2
  • Akiko Sakashita
    • 2
  • Ryutaro Kamijo
    • 1
  1. 1.Department of Biochemistry, School of DentistryShowa UniversityShinagawaJapan
  2. 2.Department of Internal MedicineShowa University Northern Yokohama HospitalTsuzuki, YokohamaJapan
  3. 3.Department of Integrative PhysiologyShiga University of Medical ScienceOtsuJapan

Personalised recommendations