BMP2 Increases Adipogenic Differentiation in the Presence of Dexamethasone, which is Inhibited by the Treatment of TNF-a in Human Adipose Tissue-Derived Stromal Cells

Lee, Sun Young; Lee, Jun Young; Kim, Jee young; Bae, Yong Chan; Suh, Kuen Tak; Jung, Jin Sup

doi:10.1159/000366341

Cited by 27 publications

(25 citation statements)

References 40 publications

(42 reference statements)

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“…In adipose‐derived stromal cells, BMP2 supports both adipogenic and osteogenic differentiation. In one study, addition of BMP2 to human adipose–derived stromal cells inhibited osteogenic differentiation in cells from six out of eight donors but enhanced it in cells from the remaining two donors . Similar inconsistencies were also seen in other studies.…”

Section: Introductionsupporting

confidence: 62%

Beyond the bone: Bone morphogenetic protein signaling in adipose tissue

Blázquez‐Medela

Jumabay

Boström³

2019

Obesity Reviews

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Summary The bone morphogenetic proteins (BMPs) belong to the same superfamily as related to transforming growth factor β (TGFβ), growth and differentiation factors (GDFs), and activins. They were initially described as inducers of bone formation but are now known to be involved in morphogenetic activities and cell differentiation throughout the body, including the development of adipose tissue and adipogenic differentiation. BMP4 and BMP7 are the most studied BMPs in adipose tissue, with major roles in white adipogenesis and brown adipogenesis, respectively, but other BMPs such as BMP2, BMP6, and BMP8b as well as some inhibitors and modulators have been shown to also affect adipogenesis. It has become ever more important to understand adipose regulation, including the BMP pathways, in light of the strong links between obesity and metabolic and cardiovascular disease. In this review, we summarize the available information on BMP signaling in adipose tissue using preferentially articles that have appeared in the last decade, which together demonstrate the importance of BMP signaling in adipose biology.

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Section: Introductionsupporting

confidence: 62%

Beyond the bone: Bone morphogenetic protein signaling in adipose tissue

Blázquez‐Medela

Jumabay

Boström³

2019

Obesity Reviews

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“…It was shown that high dose of TNF-α suppressed the osteogenic differentiation of MSC-like cells by decreased levels of alkaline phosphatase (ALP), osteocalcin (OCN), and Runx2 [16-18]. On the other hand, several studies suggest that TNF-α may have an inhibitory effect on BMP-induced osteoblast differentiation of MSCs or preosteoblastic cells [19-21]. …”

Section: Introductionmentioning

confidence: 99%

Pro-Inflammatory Cytokine TNF-α Attenuates BMP9-Induced Osteo/ Odontoblastic Differentiation of the Stem Cells of Dental Apical Papilla (SCAPs)

Wang

Jiang

Huang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs). Methods: Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment. Results: Periapical periodontitis was successfully established in rat immature permanent teeth with periapical lesions, in which TNF-α was shown to release during the inflammatory phase. BMP9-induced alkaline phosphatase activity, the expression of osteocalcin and osteopontin, and matrix mineralization in iSCAPs were inhibited by TNF-α in a dose-dependent fashion, although increased AdBMP9 partially overcame TNF-α inhibition. Furthermore, high concentration of TNF-α effectively inhibited BMP9-induced ectopic bone formation in vivo. Conclusion: TNF-α plays an important role in periapical bone defect during the inflammatory phase and inhibits BMP9-induced osteoblastic differentiation of iSCAPs, which can be partially reversed by high levels of BMP9. Therefore, BMP9 may be further explored as a potent osteogenic factor to improve osteo/odontogenic differentiation in tooth regeneration in chronic inflammation conditions.

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“…Tissue regeneration may be compromised during chronic inflammation (Matzelle et al, ). Previous studies have shown that TNF‐alpha simulates the inflammatory microenvironment and activates the Wnt canonical pathway (Chen et al, ; Huang et al, , ; Khan et al, ; Lee et al, ; Lu et al, ; Mountziaris et al, ; Mukai et al, ; Qin et al, ; Tan et al, ). In this study, we analysed the effect of TNF‐alpha and DKK1 on BMP9‐induced osteogenic differentiation both in vitro and in vivo.…”

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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BMP2 Increases Adipogenic Differentiation in the Presence of Dexamethasone, which is Inhibited by the Treatment of TNF-a in Human Adipose Tissue-Derived Stromal Cells

Cited by 27 publications

References 40 publications

Beyond the bone: Bone morphogenetic protein signaling in adipose tissue

Beyond the bone: Bone morphogenetic protein signaling in adipose tissue

Pro-Inflammatory Cytokine TNF-α Attenuates BMP9-Induced Osteo/ Odontoblastic Differentiation of the Stem Cells of Dental Apical Papilla (SCAPs)

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

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