Co-stimulation with bone morphogenetic protein-9 and FK506 induces remarkable osteoblastic differentiation in rat dedifferentiated fat cells

Nakamura, Toshiaki; Shinohara, Yukiya; Momozaki, Sawako; Yoshimoto, Takehiko; Noguchi, Kazuyuki

doi:10.1016/j.bbrc.2013.09.073

Cited by 28 publications

(29 citation statements)

References 32 publications

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“…Leblanc et al showed that BMP-9 induces heterotrophic ossification in damaged, but not undamaged skeletal muscle, whereas BMP-2 can cause it in both 10) . Moreover, it has been demonstrated that BMP-9 possesses more potent osteogenic activity than BMP-2 and is resistant to noggin, a BMP antagonist [11][12][13] . Regarding the ability of bone formation, some studies under the condition of using recombinant adenoviruses expressing BMP-9 have demonstrated that it induces robust and mature ectopic bone formation [14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects

et al. 2016

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The aim of this study was to examine the effects of recombinant human BMP-9 (rhBMP-9) with chitosan sponge (ChiS) or absorbable collagen sponge (ACS) on bone formation in rat calvarial defects. The defects were treated by one of the following implantations: ChiS, rhBMP-9/ChiS, ACS, rhBMP-9/ACS and no implantation. The animals were euthanized at 8 weeks for histological evaluation. The percentage of defect closure (DC) in the rhBMP-9/ACS group was significantly greater than that in the ACS group. The rhBMP-9/ ACS group demonstrated the highest level of DC among all the groups. The newly formed bone area (NBA) and NBA/total area in the ChiS-implanted groups and in the rhBMP-9/ACS group were significantly greater compared with those in the ACS group. It can be concluded that rhBMP-9/ACS has a potential to induce bone formation in rat calvarial defects. Further studies are required to elucidate the mechanism of bone formation induced by rhBMP-9.

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Section: Introductionmentioning

confidence: 99%

Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects

et al. 2016

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“…The difference in osteogenic behavior between BMP2 and BMP9 was addressed previously by several pathway variances according to adenovirus experiments. BMP antagonist, noggin inhibited BMP2 osteogenesis, however SMAD phosphorylation by BMP9 was not inhibited by exogenous noggin (Bergeron et al, 2009; Nakamura, Shinohara, Momozaki, Yoshimoto, & Noguchi, 2013; Wang et al, 2013). BMP3, a known BMP2 inhibitor, did not inhibit BMP9‐mediated bone formation (Kang et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Absorbable collagen sponges loaded with recombinant bone morphogenetic protein 9 induces greater osteoblast differentiation when compared to bone morphogenetic protein 2

Fujioka‐Kobayashi

Benoit

Saulačić

et al. 2017

Clinical & Exp Dental Res

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The use of growth factors for the regeneration of soft and hard tissues has been utilized extensively in dental medicine over the past decade. Recently our group found that recombinant human bone morphogenetic protein 9 (rhBMP9) was more osteopromotive than recombinant human bone morphogenetic protein 2 (rhBMP2) when combined with a deprotenized bovine bone mineral bone grafting material. The aim of the present in vitro study was to evaluate the regenerative potential of an absorbable collagen sponge(ACS) specifically designed for extraction socket healing loaded with rhBMP9 when compared to rhBMP2. The adsorption and release kinetics of rhBMP2 and rhBMP9 were first investigated by enzyme‐linked immunosorbent assay quantification. Then, the cellular effects of stromal cell line (ST2) preosteoblasts were investigated utilizing four groups including rhBMP2 and rhBMP9 at both low(10 ng/ml) and high(100 ng/ml) concentrations loaded onto ACS. Cellular attachment(8 hours) and proliferation(1, 3, and 5 days) as well as osteoblast differentiation were investigated by real‐time polymerase chain reaction (PCR) at 3 and 14 days, alkaline phosphatase (ALP) activity at 7 days, and alizarin red staining at 14 days. ACS fully adsorbed both rhBMP2 and rhBMP9 that were slowly released up to 10 days. Although neither rhBMP2 nor rhBMP9 had any effects on cell attachment or proliferation, pronounced effects were observed on osteoblast differentiation. ALP activity was increased seven‐fold with rhBMP2‐high, whereas a marked 10‐fold and 20‐fold increase was observed with rhBMP9‐low and high loaded to ACS, respectively. Furthermore, mRNA levels of collagen1, ALP, bone sialoprotein, and osteocalcin were all significantly higher for rhBMP9 when compared to control or rhBMP2 groups. Alizarin red staining further confirmed that rhBMP9‐low and high demonstrated marked increases in mineralization potential when compared to rhBMP2‐high. The results demonstrate the marked effect of rhBMP9 on osteoblast differentiation when combined with ACS in comparison to rhBMP2 at doses as much as 10 times lower. Further in vivo studies are necessary to investigate whether the regenerative potential is equally as potent.

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“…• Potent osteoinductive activity • Upregulated osteopontin, osteocalcin and ALP activity within preadipocytes • Stimulates osteoblastogenesis in conjunction with all-trans retinoic acid • All-trans retinoic acid reduced levels of BMP-9 induced PPARc, C/EBPb, C/EBPa and lipid accumulation • Combined treatment also reduced the number of adipocytes and further increased matrix mineralisation and levels of Runx2, OSX, Dlx5, osteopontin, osteocalcin and ALP • BMP-9 and FK506 both upregulated levels smad 1/5/8 phosphorylation, Runx2, osterix and bone sialoprotein in rat dedifferentiated fat cells [107][108][109][110] Vascular endothelial growth factor (VEGF)…”

Section: Potential Agents Referencementioning

confidence: 99%

“…[105] Another in-vivo study involving the use of rat dedifferentiated fat cells found that BMP-9 significantly increased Runx2, osterix and bone sialoprotein levels. [107,108] Vascular endothelial growth factor (VEGF) is a glycoprotein known to play a critical role in angiogenesis during homoeostasis, pre-and postnatal development. [109] However, VEGF has also been implicated to have a role in skeletal development and bone homoeostasis.…”

Section: Potential Agents Referencementioning

confidence: 99%

Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

Lin

Dass

2018

Journal of Pharmacy and Pharmacology

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Objectives As both adipocytes and osteoblasts originate from the same pool of mesenchymal stem cells, increasing clinical evidence has emerged of the plasticity between the two lineages. For instance, the downregulation of osteoblast differentiation and upregulation of adipogenesis are common features of conditions such as multiple myeloma, obesity and drug-induced bone loss in diabetes mellitus. However, despite in-vitro and in-vivo observations of adipocyte transdifferentiation into osteoblasts, little is known of the underlying mechanisms. Key findings This review summarises the current knowledge of this particular transdifferentiation process whereby the Wnt/b-catenin signalling pathway and Runx2 overexpression have been postulated to play a critical role. Summary Furthermore, due to the possibility of a novel therapy in the treatment of bone conditions, a number of agents with the potential to induce adipo-toosteoblast transdifferentiation have been investigated such as all-trans retinoic acid, bone morphogenetic protein-9 and vascular endothelial growth factor.

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Co-stimulation with bone morphogenetic protein-9 and FK506 induces remarkable osteoblastic differentiation in rat dedifferentiated fat cells

Cited by 28 publications

References 32 publications

Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects

Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects

Absorbable collagen sponges loaded with recombinant bone morphogenetic protein 9 induces greater osteoblast differentiation when compared to bone morphogenetic protein 2

Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

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