Effect of bone morphogenetic protein-7 on gene expression of bone morphogenetic protein-4, dentin matrix protein-1, insulin-like growth factor-I and -II in cementoblasts in vitro [In vitro učinak koštanog morfogenetskog proteina-7 na gensku ekspresiju koštanog morfogenetskog proteina-4, proteina dentinskog matriksa-1, inzulinu sličnog čimbenika rasta-I i -II u cementoblastima]

Božić, Darko and Grgurević, Lovorka and Erjavec, Igor and Razdorov, Genadij and Brkljačić, Jelena and Orlić, Iva and Plančak, Darije (2012) Effect of bone morphogenetic protein-7 on gene expression of bone morphogenetic protein-4, dentin matrix protein-1, insulin-like growth factor-I and -II in cementoblasts in vitro [In vitro učinak koštanog morfogenetskog proteina-7 na gensku ekspresiju koštanog morfogenetskog proteina-4, proteina dentinskog matriksa-1, inzulinu sličnog čimbenika rasta-I i -II u cementoblastima]. Collegium Antropologicum, 36 (4). pp. 1265-1271. ISSN 0350-6134

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Abstract

Formation of root cementum is a crucial moment in the development of the periodontium. Cells that produce the cementum are named cementoblasts and they posses some unique characteristics, which differentiates them from osteoblasts. Bone morphogenetic proteins (BMPs) are crucial regulators of both bone and tooth formation. In animal studies BMPs have shown to induce periodontal regeneration, however the molecular mechanism as how BMP-7 induces cementogenesis is largely unknown. We have investigated how BMP-7 regulates gene expression of BMP-4, Dentin matrix protein-1 (DMP-1), Insulin-like growth factor-I (IGF-I) and -II (IGF-II) in cementoblasts. BMP-7 induced proliferation, and mineralized nodule formation of cementoblasts. Our results show that gene expression was influenced by the BMP-7 concentration used, with 75 ng/mL generally down-regulating gene expression at 6 hours and then up-regulating after 24 hours. The 300 ng/mL concentration had an opposite effect while the 150 ng/mL concentration generally up-regulated gene expression after 6 hours and then after 24 hours maintained this up-regulation or had no effect compared to control, depending on the examined gene. The results show that BMP-7 down-regulated BMP-4 expression in cementoblasts but still up-regulated DMP-1 gene expression suggesting that BMP-7 can, in a paracrine manner, functionally substitute for BMP-4. Furthermore, it seems that BMP-7 exerts its effect more through the IGF-II than the IGF-I pathway as shown by an up-regulation of IGF-II and down-regulation of IGF-I. These results suggest that a combination of BMP-7/IGF-II could have a potential therapeutical significance in inducing cementogenesis and periodontal regeneration.

Abstract in Croatian

Stvaranje cementa korijena ključan je moment u razvoju parodonta. Stanice koje proizvode cement nazivaju se cementoblastima i posjeduju neke jedinstvene osobine koje ih razlikuju od osteoblasta. Koštani morfogenetski proteini (BMP) važni su regulatori stvaranja kosti i zuba. Istraživanja na životinjama pokazala su da BMP potiču regeneraciju parodonta. Ipak molekularni mehanizmi kako BMP-7 potiče cementogenezu u potpunosti su nepoznati. Ispitali smo kako BMP-7 regulira gensku ekspresiju BMP-4, DMP-1, IGF-I i -II u cementoblastima. BMP-7 potiče proliferaciju te stvaranje mineraliziranih čvorića u cementoblastima. Rezultati pokazuju da je genska ekspresija bila ovisna o koncentraciji BMP-7 gdje je općenito 75 ng/mL smanjilo ekspresiju nakon 6 sati, a onda povećalo nakon 24 sata. Koncentraciju od 300 ng/mL imala je suprotan učinak, dok je koncentracija od 150 ng/mL nakon 6 sati povećala ekspresiju gena te ju nakon 24 sata zadržala povećanom ili nije imala učinka u usporedbi s kontrolom ovisno o kojem se genu radilo. Rezultati pokazuju da BMP-7 smanjuje ekspresiju BMP-4 ali povećava ekspresiju DMP-1 sugerirajući da BMP-7 može funkcionalno nadomjestiti BMP-4. Nadalje, čini se da BMP-7 djeluje više preko IGF-II nego IGF-I puta tako što povisuje ekspresiju IGF-II a smanjuje ekspresiju IGF-I. Ovi rezultati sugeriraju da kombinacija BMP-7/IGF-II može imati potencijalnu terapijsku važnost u poticanju cementogeneze i regeneraciji parodonta.

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