IGF1 potentiates BMP9-induced osteogenic differentiation in mesenchymal stem cells through the enhancement of BMP/Smad signaling

Chen, Liang; Zou, Xiang; Zhang, Ranxi; Pi, Chang-Jun; Wu, Nanping; Liang, Yin; Deng, Zhong‐Liang

doi:10.5483/bmbrep.2016.49.2.228

Cited by 40 publications

(35 citation statements)

References 37 publications

(63 reference statements)

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“…As the most potent osteogenic BMP member, it was reported that many factors or signal pathways are involved in the regulation of BMP9-induced osteogenic differentiation in MSCs, such as IGFs, GH, COX-2, and retinoic acid signals. 7,8,11,12 The Wnt pathway is another essential signal pathway that regulates the cell fate, proliferation, and differentiation during embryonic and postnatal development. It includes both canonical and noncanonical Wnt pathways, dependent on their physiological functions.…”

Section: Discussionmentioning

confidence: 99%

Wnt11 promotes BMP9‐induced osteogenic differentiation through BMPs/Smads and p38 MAPK in mesenchymal stem cells

Zhu

Liao

et al. 2018

J of Cellular Biochemistry

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Bone morphogenetic protein 9 (BMP9), as one of the most potent osteogenic factors, is a promising cytokine for bone tissue engineering. Wnt11 can regulate the development of the skeletal system and is related to high bone mass syndrome. However, the effect of Wnt11 on BMP9-induced osteogenic differentiation remains unknown. In this study, we investigated the relationship between Wnt11- and BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs). We recapitulated the osteogenic potential of BMP9 in C3H10T1/2 cells. The messenger RNA expression of Wnt11 is detectable in the available progenitor cells, and BMP9 can obviously increase the protein level of Wnt11 in these cells. Exogenous Wnt11 potentiates the effect of BMP9 on increasing alkaline phosphatase (ALP) activities, the expression of osteopontin (OPN), and Runt-related transcription factor 2 (Runx2), so does matrix mineralization in C3H10T1/2 cells. Although Wnt11 cannot increase the BMP9-induced ectopic bone formation, it can increase the bone density induced by BMP9 apparently. Wnt11 increases the level of p-Smad1/5/8, as well as p-p38. Meanwhile, Wnt11 promotes the effect of BMP9 on increasing the levels of p-Smad1/5/8 and p-p38. Inhibition of p38 decreases the BMP9-induced ALP activities, the expression of OPN, and the mineralization in C3H10T1/2 cells. However, all of these effects of the p38 inhibitor on BMP9-induced osteogenic markers can be almost reversed by the overexpression of Wnt11. Our findings suggested that Wnt11 can enhance the osteogenic potential of BMP9 in MSCs, and this effect may be partly mediated through enhancing BMPs/Smads and the p38 MAPK signal, which was induced by BMP9.

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Section: Discussionmentioning

confidence: 99%

Wnt11 promotes BMP9‐induced osteogenic differentiation through BMPs/Smads and p38 MAPK in mesenchymal stem cells

Zhu

Liao

et al. 2018

J of Cellular Biochemistry

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“…DKK1 can inhibit osteogenic differentiation, ALP activity, calcium deposition in BMP9‐induced mesenchymal stem cells and ectopic osteogenesis in nude mice (Duan & Bonewald, ; Khan et al, ; Lee et al, ; Lin et al, ). BMP receptors and P‐Smad1/5/8 are essential signalling mediators of the BMP signalling pathway (Chen et al, ; Li et al, ). Binding of BMP type I and type II receptors can induce phosphorylation of Smad1/5/8.…”

Section: Discussionmentioning

confidence: 99%

DKK1 and TNF‐alpha influence osteogenic differentiation of adBMP9‐infected‐rDFCs

Chen

Jing

et al. 2019

Oral Diseases

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Objectives Rat dental follicle cells (rDFCs) function as precursor cells of periodontal tissues. Bone morphogenetic protein (BMP9) plays an important role in proliferation and differentiation. Tumour necrosis factor‐alpha (TNF‐alpha) is an important contributor to bone resorption. Wnt canonical pathway can be inhibited by Dickkopf 1 (DKK1). The aim of the study was to enhance the osteogenesis of BMP9 treated rDFCs in an inflammatory environment and elucidate the mechanism. Materials and Methods rDFCs were infected by adenoviruses expressing BMP9 (adBMP9). Expression levels of proteins and genes were measured by Western blotting and qPCR. The effect on osteogenesis was evaluated by measuring the activity of alkaline phosphatase (ALP), observation of Alizarin Red S and haematoxylin and eosin staining. Results TNF‐alpha activated the canonical Wnt pathway and inhibited the non‐canonical pathway. DKK1 suppressed the canonical pathway and promoted the non‐canonical pathway. Addition of TNF‐alpha or DKK1 inhibited BMP9/Smad pathway. However, this inhibition was reduced by the addition of DKK1 with TNF‐alpha. Conclusions DKK1 reduces the inhibitory effects of TNF‐alpha in adBMP9‐infected‐rDFCs, possibly through interaction with the Smad signalling pathway and Wnt pathways. These findings may lead to a novel approach for the treatment of periodontitis‐related alveolar bone defects.

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“…The doses of growth factors used in the experiments are expressed as nanomolar concentrations ( in vitro experiments) or picomoles ( in vivo experiment) due to the different molecular masses of BMP‐2 and BMP‐6. These doses were based on previously published studies …”

Section: Methodsmentioning

confidence: 99%

“…Recent studies have shown that IGF‐1 is able to enhance the osteogenic potential of BMP‐2 or other BMPs such as −7 or −9 in vitro . However, no attempts on analyzing the osteogenic effect of combining IGF‐1 with BMP‐6 have been made, even though the latter is known to preferentially use a different set of BMP receptors than BMP‐2, while being one of the most potent members of the BMP family .…”

Section: Introductionmentioning

confidence: 99%

Insulin‐like growth factor‐1 (IGF‐1) enhances the osteogenic activity of bone morphogenetic protein‐6 (BMP‐6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF‐1 is combined with BMP‐2

Rico-Llanos

Becerra

Visser

2017

J Biomedical Materials Res

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Bone morphogenetic protein-2 (BMP-2) is widely used in orthopedic surgery and bone tissue engineering because of its strong osteogenic activity. However, BMP-2 treatments have several drawbacks and many groups are actively exploring alternatives. Since BMP-6 has been demonstrated to be more osteoinductive, its use, either alone or together with other growth factors, might be an interesting option. In this work, we have compared the effect of BMP-2, BMP-6, or insulin-like growth factor-1 (IGF-1), either alone or in combination. Murine preosteoblasts were treated with 15 nM IGF-1 and/or 6 nM BMP-2 or -6 and the expression of osteogenic marker genes, proliferation, and alkaline phosphatase (ALP) activity in vitro were analyzed. The results showed that IGF-1 greatly enhanced the BMP-induced osteogenic differentiation of these cells in general and that the ALP activity in the cultures was higher when the combination was made with BMP-6 than with BMP-2. Furthermore, we tested the osteogenic potential of these treatments in vivo by loading 25 pmoles of IGF-1 and/or 10 pmoles of BMP-2 or -6 onto absorbable collagen sponges and implanting them into an ectopic bone formation model in rats. This study revealed that only BMP-6 was able to induce bone formation at the used dose and that the addition of IGF-1 contributed to an increase of the mineralization in the implants. Hence, the combination of BMP-6 with IGF-1 might be a better alternative than BMP-2 for orthopedic surgery or bone tissue engineering approaches. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1867-1875, 2017.

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IGF1 potentiates BMP9-induced osteogenic differentiation in mesenchymal stem cells through the enhancement of BMP/Smad signaling

Cited by 40 publications

References 37 publications

Wnt11 promotes BMP9‐induced osteogenic differentiation through BMPs/Smads and p38 MAPK in mesenchymal stem cells

Wnt11 promotes BMP9‐induced osteogenic differentiation through BMPs/Smads and p38 MAPK in mesenchymal stem cells

DKK1 and TNF‐alpha influence osteogenic differentiation of adBMP9‐infected‐rDFCs

Insulin‐like growth factor‐1 (IGF‐1) enhances the osteogenic activity of bone morphogenetic protein‐6 (BMP‐6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF‐1 is combined with BMP‐2

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