Stimulation of Smad1 Transcriptional Activity by Ras-Extracellular Signal-Regulated Kinase Pathway: A Possible Mechanism for Collagen-Dependent Osteoblastic Differentiation

Suzawa, Miyuki; Tamura, Yasuhiro; Fukumoto, Seiji; Miyazono, Kohei; Fujita, Toshiro; Kato, Shigeaki; Takeuchi, Yasuhiro

doi:10.1359/jbmr.2002.17.2.240

Cited by 87 publications

(86 citation statements)

References 41 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These characteristics facilitate the ingrowth and remodeling of new bone in vivo. The cooperation between BMP-2, collagen, and noncollagenous proteins plays an important role in the differentiation of BMSCs to osteoblasts and osteoinduction in vivo (Globus et al 1995, Schneider et al 2001, Suzawa et al 2002, Xiao et al 2002. In this study, we found that self-secreted ECM served as a good carrier for BMSCs in the repair of segmental tibial bone defects in goats, although selfsecreted ECM has little osteoconductivity.…”

Section: Discussionmentioning

confidence: 49%

Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats

Tang

Dai

et al. 2005

Acta Orthopaedica

View full text Add to dashboard Cite

(2005) Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats, Acta Orthopaedica, 76:5, 637-646, DOI: 10.1080 Background Tissue-engineered bone may be used for filling bone defects. There are, however, no reports on this technique used in large animals.Methods We evaluated the effectiveness of, and immune response in repairing diaphyseal bone defects by gene transfer using bone morphogenetic proteins (BMPs). We used adenovirus-mediated human BMP-2 (Adv-hBMP-2) gene-transduced bone marrow stromal cells (BMSCs) to repair 2.1-cm segmental tibial bone defects in goats (group I, n = 7). An Adv-ßgal-transduced BMSC group (group II, n = 5), a non-transduced BMSC group (group III, n = 5), and an untreated group (group IV, n = 2) were used as controls. Self-secreted extracellular matrix was used as cellular carrier.Results Radiographic and histomorphometric examination demonstrated more callus in the bone defects of group I compared to other groups.Week 24 after implantation, the defect healing rates of groups I, II, III, and IV were 6/7, 1/5, 2/5, and 0/2, respectively. The maximum compressive strength of new tissue in the bone defects of group I was higher than those of groups II and III. Temporary cellular and persistent humoral immune responses against adenovirus were detected after hBMP-2 gene transfer.Interpretation We found that Adv-hBMP-2 genetransduced BMSCs had superior osteoinductivity in the repair of tibial bone defects in goats, but it could cause temporary cellular and persistent humoral immune responses against adenovirus.

show abstract

Section: Discussionmentioning

confidence: 49%

Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats

Tang

Dai

et al. 2005

Acta Orthopaedica

View full text Add to dashboard Cite

show abstract

“…On the other hand, stimulation of mouse MSC and murine preosteoblasts MC3T3-E1 cells with BMP-2 also promoted both ERK expression and ERK activity 12) . Reducing ERK activity decreased ALP activity, suggesting that BMP-2 induced ERK activation and that this ERK activation is required for ALP activation 29,30) . These contradictory reports indicated that the effects of BMP-2 on osteogenic differentiation are regulated by MAPK signaling pathways but that their mechanism of regulation is very complicated and is still not well understood.…”

Section: Discussionmentioning

confidence: 99%

Requirement for JNK and ERK Activation in BMP-2/BMP-7 -Induced Osteogenesis of Human Periodontal Ligament Cells

Tezen

Ochiai

Aida

et al. 2012

J. Hard Tissue Biology.

View full text Add to dashboard Cite

The BMP-2/BMP-7 heterodimer (BMP-2/-7) is a potent osteogenic inducer. It is well established that BMP-2/-7 activates mitogen activated protein kinases (MAPKs) in some cells. It is also widely accepted that MAPK signaling cascades play a crucial role in the immediate osteogenic response to BMPs. However, the precise mechanism and role of the MAPK signaling network in osteogenesis is still controversial since there are many kinds of BMP receptors (BMPR) whose signal transduction is very complex and whose signals differ from cell to cell. We investigated whether BMP-2/-7 regulates osteogenic gene expression in human periodontal ligament (HPDL) cells, and how MAPKs might be involved in this process, by treatment of HPDL cells with BMP-2/-7 with or without MAPK inhibitors. We found that the Jun-N-terminal kinase (JNK) is essential for the expression of almost all osteogenic marker genes. Inhibition of extracellular signal-regulated kinase (ERK) using inhibitor had no effect on the expression of early osteogenic marker genes, whereas it significantly downregulated the expression of late osteogenic marker genes such as Bone sialopotein and Osteocalcin. These results indicate that MAPKs play a crucial role in osteogenesis of HPDL cells.

show abstract

“…Integrin activation of focal adhesion kinase (FAK) induces Ras and the downstream Erk in ostoeblasts. FAK activated Ras-Erk stimulates Smad-1 activity in response to BMP-2 in osteoblasts (Suzawa et al, 2002). The Ras-Erk-signaling pathway is activated by serum.…”

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 2 stimulation of tumor growth involves the activation of Smad-1/5

2005

View full text Add to dashboard Cite

Morphogenetic protein 2 (BMP-2) is normally expressed in the embryo promoting the development of several organs. Aberrant expression of BMP-2 occurs in approximately 98% of lung carcinomas, however, its role in regulating tumor growth is poorly understood. We show that BMP-2 induces Id-1 expression in lung cancer cell lines through its activation of Smad-1/5, which is dependent on cell culture conditions. A549 cells in DMEM/5% FCS BMP-2 activated Smad-1/5 and caused a transient increase in proliferation. In serum-free medium, BMP-2 induced significantly less Smad-1/5 activation and Id-1 expression, and produced significant growth inhibition. The affect of BMP-2 on tumor growth in vivo was substantially more significant. Recombinant BMP-2 coinjected with A549 cells, into nude mice increased proliferation and produced an increase in Id-1 expression. Forced expression of BMP-2 in A549 cells significantly enhanced tumor growth in the lungs following intravenous injection but not of subcutaneous tumors. Tumors in the lung were found to have an activated Smad-1/5 and expressed Id-1. Subcutaneous tumors expressed less activated Smad-1/5 and Id-1 than that of controls. Human lung carcinomas were also found to express an activated Smad-1/5 and Id-1. We provide evidence that BMP-2 promotes tumor growth. This paper highlights that cell culture experiments may not reveal the full biological affects of BMP-2, and its activity varies depending of the local environment.

show abstract

Stimulation of Smad1 Transcriptional Activity by Ras-Extracellular Signal-Regulated Kinase Pathway: A Possible Mechanism for Collagen-Dependent Osteoblastic Differentiation

Abstract: ABSTRACT

Cited by 87 publications

References 41 publications

Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats

Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats

Requirement for JNK and ERK Activation in BMP-2/BMP-7 -Induced Osteogenesis of Human Periodontal Ligament Cells

Bone morphogenetic protein 2 stimulation of tumor growth involves the activation of Smad-1/5

Contact Info

Product

Resources

About