Bone morphogenetic protein-2 stimulates alkaline phosphatase activity and collagen synthesis in cultured osteoblastic cells, MC3T3-E1

Takuwa, Yoh; Ohse, Chizuko; Wang, Elizabeth A.; Wozney, John M.; Yamashita, Kamejiro

doi:10.1016/0006-291x(91)90490-x

Cited by 287 publications

(160 citation statements)

References 8 publications

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“…Based on this release rate 5 mg of microparticles (as used in vitro) will release on average 18.5 ng of BMP-2 daily. This is above the lower limits shown to induce alkaline phosphatase (ALP) expression in MC3T3-E1 cells [37]. …”

Section: Microparticle Characterisation and Analysismentioning

confidence: 80%

PLGA-Based Microparticles for the Sustained Release of BMP-2

et al. 2011

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Abstract:The development of growth factor delivery strategies to circumvent the burst release phenomenon prevalent in most current systems has driven research towards encapsulating molecules in resorbable polymer matrices. For these polymer release techniques to be efficacious in a clinical setting, several key points need to be addressed. This present study has investigated the encapsulation of the growth factor, BMP-2 within PLGA/PLGA-PEG-PLGA microparticles. Morphology, size distribution, encapsulation efficiency and release kinetics were investigated and we have demonstrated a sustained release of bioactive BMP-2. Furthermore, biocompatibility of the PLGA microparticles was established and released BMP-2 was shown to promote the differentiation of MC3T3-E1 cells towards the osteogenic lineage to a greater extent than osteogenic supplements (as early as day 10 in culture), as determined using alkaline phosphatase and alizarin red assays. This study showcases a potential BMP-2 delivery system which may OPEN ACCESSPolymers 2011, 3 572 now be translated into more complex delivery systems, such as 3D, mechanically robust scaffolds for bone tissue regeneration applications.

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Section: Microparticle Characterisation and Analysismentioning

confidence: 80%

PLGA-Based Microparticles for the Sustained Release of BMP-2

et al. 2011

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“…ALP is an important early marker of osteoblast differentiation (Kim et al 2004, ten Dijke et al 2003 which controls the precipitation of hydroxyapatite crystals in the early phase of mineralization in bone formation process (Anderson 2003, Manolagas 2000. Moreover, Chaudhary et al (2004) have reported that the ALP activity is closely associated with the formation of mineralized matrix while OCN, BGN and COL1A2 are major proteins commonly found in extracellular bone matrix and are believed to play an important role in bone formation (Chen et al 2003, 2004, Kuroki et al 1994, Parisuthiman et al 2005, Pischon et al 2004, Regazzoni et al 2001, Sierra et al 2003, Takeuchi et al 1996, Takuwa et al 1991, Viereck et al 2002, Young et al 2002.…”

Section: Discussionmentioning

confidence: 99%

Highly osteogenic PDL stem cell clones specifically express elevated levels of ICAM1, ITGB1 and TERT

Sununliganon

Singhatanadgit

2011

Cytotechnology

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Cells derived from the periodontal ligament (PDL) have previously been reported to have stem cell-like characteristics (PDL stem cells; PDLSCs) and play an important part in bone engineering, including that of alveolar bone. However, these populations have been heterogeneous, and thus far no specific marker has yet been established from adult human stem cells derived from PDL tissue. We have previously isolated highly purified single cellderived PDLSC clones and delineated their phenotypic and functional characteristics. In this report, we further obtained three homogeneous and distinct PDLSC clones demonstrating low, moderate and high mineralized matrix forming ability-namely PC12, PC4 and PC3, respectively, and the expression of mesenchymal stem cell pathway-specific genes in these clones was investigated. PCR array revealed that the expression of intercellular adhesion molecule 1 (ICAM1), integrin beta 1 (ITGB1) and telomerase reverse transcriptase (TERT) was associated with highly osteogenic PDLSC clones, as determined by the expression of key osteoblastic markers and their ability to form alizarin red S positive mineralized matrix in vitro. The present results suggest that these three mesenchymal stem cell-associated markers could potentially be used to isolate PDLSCs with high osteogenic capability for engineering new bone.

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“…BMPs play an important role in the formation and remodeling of bone by stimulating the differentiation of osteoblast cells (10,31). In the BMP subfamily, BMP-2, which is synthesized and secreted into the extracellular by osteoblasts, has demonstrated a strong osteo-inductive capacity in vivo and in vitro (6,7). The action of BMPs is mediated by hetero-tetrameric serine/threonine kinase receptors and the downstream transcription factors Smad1/5/8.…”

Section: Discussionmentioning

confidence: 99%

“…Among cell signaling pathways associated with bone formation, bone morphogenetic proteins (BMPs) play important roles in bone formation and osteoblasts differentiation by stimulating alkaline phosphatase (ALP) activity and synthesis of proteoglycan, collagen, fibronectin and osteocalcin (3)(4)(5). In the BMP subfamily, BMP-2 has demonstrated a strong osteo-inductive capacity in vivo and in vitro (6,7). It transduces signals through Smad-dependent and Smad-independent signalling pathways (8).…”

Section: Introductionmentioning

confidence: 99%

Astragaloside II induces osteogenic activities of osteoblasts through the bone morphogenetic protein-2/MAPK and Smad1/5/8 pathways

et al. 2012

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Abstract. Radix Astragalus has been identified to exert beneficial effects in preventing postmenopausal bone loss. However, the active ingredients and mechanism of action remain unknown. In this study, we examined the effect of Astragaloside II (AST II), which is a monomer of Astragalus saponin, on the viability, proliferation, differentiation and maturation of rat primary osteoblasts, as well as its relevant molecular mechanism. We found that AST II exhibits a significant induction of proliferation, differentiation and mineralization in primary osteoblasts. AST II stimulates osteoblast differentiation at various stages, from early to late stage of differentiated osteoblasts. Furthermore, induction of differentiation by AST II is associated with increased expression of bone morphogenetic protein-2 (BMP-2), activation of Smad1/5/8, ERK1/2 and p38, and increased expression of core-binding factor 1 (Cbfa1)/Runx2. BMP antagonist (Noggin) blocks the effect of AST II on cell differentiation, and Smad1/5/8, p38, Cbfa1 expression, but only partly decreases ERK1/2 activation. This indicates that BMP-2 is essential in AST II-mediated osteoblast differentiation and Smad1/5/8, p38, Cbfa1 activation, and is partly involved in ERK1/2 activation. In conclusion, although in vivo studies are required in the future, as a phyto-saponin of Radix Astragalus, AST II may become a novel candidate that is beneficial for stimulating the osteoblastic activity resulting in bone formation, which has not been recognized and reported previously.

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Bone morphogenetic protein-2 stimulates alkaline phosphatase activity and collagen synthesis in cultured osteoblastic cells, MC3T3-E1

Cited by 287 publications

References 8 publications

PLGA-Based Microparticles for the Sustained Release of BMP-2

PLGA-Based Microparticles for the Sustained Release of BMP-2

Highly osteogenic PDL stem cell clones specifically express elevated levels of ICAM1, ITGB1 and TERT

Astragaloside II induces osteogenic activities of osteoblasts through the bone morphogenetic protein-2/MAPK and Smad1/5/8 pathways

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