BMP OSTEOGENESIS MSC · Mechanisms of recombinant human bone morphogenetic protein 2 - mediated osteogenesis of human bone marrrow stromal cells: regulatory signaling pathways and effect of aging
6РП — Действия „Мария Кюри“
- Период
- 2007-03-01 → 2009-02-28
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите.
Накратко на български
Механизмите, чрез които протеинът BMP2 стимулира образуването на кост от стволови клетки, се анализират при млади и възрастни донори. Това помага да се разбере защо някои пациенти реагират различно на терапията и защо при хората са нужни по-високи дози от при животните.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Цел на проекта
We propose to investigate mechanisms by which bone morphogenetic protein 2 mediates osteogenesis in human bone marrow stromal cell cultures. Bone morphogenetic proteins (BMPs) are currently considered promising bone therapeutic agents because of their bone forming capacity in several animal models. Recombinant forms of BMP2 and 7 have been approved for the promotion of spinal fusions, treatment of open fractures and fracture non-unions. Other musculoskeletal applications of BMPs in humans have been less successful; some reports indicate large variations in response among individual patients and the need for much higher BMP doses to induce adequate bone formation in humans compared with animals.One part of the problem may be poor osteogenic response of adult human bone marrow stromal cells (hMSC) to BMPs. Bone marrow stroma is a reservoir of osteoblast precursors, which can be induced to differentiate into osteoblasts upon demand. Our hypothesis is that BMP-mediated osteogenesis of hMSC from mature donors is negatively regulated by serum-induced high ERK activity and positively regulated by insulin or IGF-1 induced PI3-K signalling, while BMP-2 mediated osteogenic progression of hMSC from paediatric donors is less dependent on these co-regulatory pathways. Aim 1 tests the hypothesis that serum-activated ERK phosphorylates BMP-activated Smads, thus preventing Smad nuclear localization and transcriptional activity. Aim 2 investigates mechanisms by which the insulin/IGF-1 pathway interacts with the BMP signalling pathways to promote osteogenesis. Aim 3 tests the hypothesis that hMSC from young donors are less susceptible to ERK and PI3-K co-regulatory signalling, thus they are capable of BMP-mediated osteogenesis in a broader range of environments. We expect the results of this study to provide possible explanations for the frustrating results of some clinical trials and suggest potential approaches for improving the therapeutic efficacy of BMPs.
Оригинален текст от CORDIS (на английски).
Участници
- JAGIELLONIAN UNIVERSITY · KRAKOWКоординаторПолша
Връзки
Данни: CORDIS, © Европейски съюз