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Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice
International Orthopaedics, 39 (2015), 1; 161-172. https://doi.org/10.1007/s00264-014-2550-4
Pauk, Martina; Grgurević, Lovorka; Brkljačić, Jelena; Kufner, Vera; Bordukalo-Nikšić, Tatjana; Grabušić, Kristina; Razdorov, Genadij; Rogić, Dunja; Žuvić, Marijan; Oppermann, Hermann; Babitt, Jodie L.; Lin, Herbert Y.; Volarević, Siniša; Vukičević, Slobodan

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Pauk, M., Grgurević, L., Brkljačić, J., Kufner, V., Bordukalo Nikšić, T., Grabušić, K. ... Vukičević, S. (2015). Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice. International Orthopaedics, 39. (1), 161-172. doi: 10.1007/s00264-014-2550-4

Pauk, Martina, et al. "Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice." International Orthopaedics, vol. 39, br. 1, 2015, str. 161-172. https://doi.org/10.1007/s00264-014-2550-4

Pauk, Martina, Lovorka Grgurević, Jelena Brkljačić, Vera Kufner, Tatjana Bordukalo Nikšić, Kristina Grabušić, Genadij Razdorov, et al. "Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice." International Orthopaedics 39, br. 1 (2015): 161-172. https://doi.org/10.1007/s00264-014-2550-4

Pauk, M., et al. (2015) 'Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice', International Orthopaedics, 39(1), str. 161-172. doi: 10.1007/s00264-014-2550-4

Pauk M, Grgurević L, Brkljačić J, Kufner V, Bordukalo Nikšić T, Grabušić K, i sur.. Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice. International Orthopaedics [Internet]. 2015. [pristupljeno 19.12.2024.];39(1):161-172. doi: 10.1007/s00264-014-2550-4

M. Pauk, et al., "Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice", International Orthopaedics, vol. 39, br. 1, str. 161-172, 2015. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:105:857211. [Citirano: 19.12.2024.]

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Podaci o radu
Naslov (engleski)Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice
AutorMartina Pauk
AutorLovorka Grgurević
AutorJelena Brkljačić
AutorVera Kufner
AutorTatjana Bordukalo-Nikšić
AutorKristina Grabušić
AutorGenadij Razdorov
AutorDunja Rogić
AutorMarijan Žuvić
AutorHermann Oppermann
AutorJodie L. Babitt
AutorHerbert Y. Lin
AutorSiniša Volarević
AutorSlobodan Vukičević
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Temeljne medicinske znanosti
Sažetak (engleski)
PURPOSE: Iron overload accelerates bone loss in mice lacking the bone morphogenetic protein 6 (Bmp6) gene, which is the key endogenous regulator of hepcidin, iron homeostasis gene. We investigated involvement of other BMPs in preventing haemochromatosis and subsequent osteopenia in Bmp6-/- mice. ----- METHODS: Iron-treated wild-type (WT) and Bmp6-/- mice were analysed for hepcidin messenger RNA (mRNA) and tissue and blood BMP levels by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunohistochemistry, Western blot, enzyme-linked immunosorbent assay (ELISA) and proximity extension assay. BMPs labeled with technetium-99m were used in pharmacokinetic studies. ----- RESULTS: In WT mice, 4 h following iron challenge, liver Bmp6 and hepcidin expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that BMP6 circulates in WT mice and that iron increased the BMP6 serum level and the specific liver uptake of (99m)Tc-BMP6. In Bmp6-/- mice, iron challenge led to blunted activation of liver Smad signaling and hepcidin expression with a delay of 24 h, associated with increased Bmp5 and Bmp7 expression and increased Bmp2, 4, 5 and 9 expression in the duodenum. Liver Bmp7 expression and increased circulating BMP9 eventually contributed to the late hepcidin response. This was further supported by exogenous BMP7 therapy resulting in an effective hepcidin expression followed by a rapid normalisation of plasma iron values and restored osteopenia in Bmp6-/- mice. ----- CONCLUSION: In Bmp6-/- mice, iron activated endogenous compensatory mechanisms of other BMPs that were not sufficient for preventing hemochromatosis and bone loss. Administration of exogenous BMP7 was effective in correcting the plasma iron level and bone loss, indicating that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran
Verzija publikacijeZavršna verzija rukopisa prihvaćena za objavljivanje (postprint)
Naslov časopisaInternational Orthopaedics
Brojčani podacivol. 39, br. 1, str. 161-172
p-ISSN0341-2695
DOIhttps://doi.org/10.1007/s00264-014-2550-4
URN:NBNurn:nbn:hr:105:857211
Datum objave publikacije2015
URL dokumentahttp://doi.org/10.1007/s00264-014-2550-4
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
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Datum i vrijeme pohrane2024-03-28 08:13:46