2,4,5-Trimethoxyldalbergiquinol promotes osteoblastic differentiation and mineralization via the BMP and Wnt/β-catenin pathway

Hm, Yun; Kr, Park; Th, Quang; Oh, Hyuncheol; Jt, Hong; Yc, Kim; Ec, Kim

doi:10.1038/cddis.2015.185

Cited by 80 publications

(66 citation statements)

References 40 publications

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“…MAP kinases and NF-jB are essential for the induction of osteoblast differentiation-related genes via the activation of distinct cascades that target specific transcription factors, such as Runx2 [57,62]. In this study, rh-SHH-induced activation of Akt, p38, ERK, JNK, and NF-jB was attenuated by noggin, BMP-2 siRNA, and Cy.…”

Section: Discussionmentioning

confidence: 73%

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Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways

et al. 2016

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Although sonic hedgehog (SHH), an essential molecule in embryogenesis and organogenesis, stimulates proliferation of human periodontal ligament (PDL) stem cells, the effects of recombinant human SHH (rh-SHH) on osteoblastic differentiation are unclear. To reveal the role of SHH in periodontal regeneration, expression of SHH in mouse periodontal tissues and its effects on the osteoblastic/cementoblastic differentiation in human cementoblasts were investigated. SHH is immunolocalized to differentiating cementoblasts, PDL cells, and osteoblasts of the developing mouse periodontium. Addition of rh-SHH increased cell growth, ALP activity, and mineralization nodule formation, and upregulated mRNA expression of osteoblastic and cementoblastic markers. The osteoblastic/cementoblastic differentiation of rh-SHH was abolished by the SHH inhibitor cyclopamine (Cy) and the BMP antagonist noggin. rh-SHH increased the expression of BMP-2 and -4 mRNA, as well as levels of phosphorylated Akt, ERK, p38, and JNK, and of MAPK and NF-κB activation, which were reversed by noggin, Cy, and BMP-2 siRNA. Collectively, this study is the first to demonstrate that SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway. Thus, SHH plays important roles in the development of periodontal tissue, and might represent a new therapeutic target for periodontitis and periodontal regeneration.

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Section: Discussionmentioning

confidence: 73%

“…The role of the BMP signaling pathway has been reported in osteoblastic/cementoblast differentiation [6,57]. Noggin directly binds to BMP-2, thereby preventing its interaction with BMP receptor [58].…”

Section: Discussionmentioning

confidence: 99%

Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways

et al. 2016

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“…The nuclear localization, structural modification, and stabilization of β-catenin also served as an important part in osteoblast differentiation. 36 Furthermore, our study also showed that activated Wnt and BMP signaling pathways could upregulate the EMX2 expression, induce calcium salt deposition, increase mineralized nodules, and enhance ALP activity, thereby accelerating the process of MSCs differentiating into osteoblasts. 32 Increased expression of ALP, Col I, OPN, OPG/RANKL, and Runx2 played an important role in inducing osteoblast differentiation by activating the BMP and Wnt/β-catenin signaling pathways.…”

Section: Discussionmentioning

confidence: 54%

Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

Wei

Chen

et al. 2018

J of Cellular Biochemistry

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Osteoblast differentiation, defined as the process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, is directly linked to multiple myeloma (MM) bone disease. Wnt and bone morphogenetic protein (BMP) are proved to be implicated in the pathological or defective osteoblast differentiation process. This study aims to test the involvement of Wnt, bone morphogenetic proteins (BMP) pathways, and empty spiracles homeobox 2 (EMX2) in osteoblast differentiation and MM development. Initially, differentially expressed genes in bone marrow mesenchymal stem cells (MSCs) from MM patients and healthy donors were identified using microarray‐based gene expression profiling. The functional role of Wnt and BMP in MM was determined. Next, we focused on the co‐operative effects of Wnt and BMP on calcium deposition, alkaline phosphatase (ALP) activity, the number of mineralized nodules, and osteocalcin (OCN) content in MSCs. The expression patterns of Wnt and BMP pathway–related genes, EMX2 and osteoblast differentiation‐related factors were determined to assess their effects on osteoblast differentiation. Furthermore, regulation of Wnt and BMP in ectopic osteogenesis was also investigated in vivo. An integrated genomic screen suggested that Wnt and BMP regularly co‐operate to regulate EMX2 and affect MM. EMX2 was downregulated in MSCs. The activated Wnt and BMP resulted in more calcium salt deposits, mineralized nodules, and a noted increased in ALP activity and OCN content by upregulating EMX2, leading to induced differentiation of MSCs into osteoblasts. Collectively, this study demonstrated that Wnt and BMP pathways could co‐operatively stimulate differentiation of MSCs into osteoblasts and inhibit MM progression, representing potential targets for MM treatment.

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“…Mineralized nodule is typically observed as a late phase marker for terminal differentiation. MSCs can be stained for mineral deposition by Alizarin red [24]. Here we noted the negative impact of Osthole on the development of mineralized nodules by detecting the calcium influx with Fluo4-AM probe.…”

Section: The Influence Of Osthole Removal On Osteoblast Differentiationmentioning

confidence: 98%

An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/β-Catenin and Erk1/2-MAPK Pathways

Chen

Dai

et al. 2016

Cell Physiol Biochem

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Background/Aims: Bone marrow-derived mesenchymal stem cells (MSCs) are responsible for new bone formation during adulthood. Accumulating evidences showed that Osthole promotes the osteogenic differentiation in primary osteoblasts. The aim of this study was to investigate whether Osthole exhibits a potential to stimulate the osteogenic differentiation of MSCs and the underlying mechanism. Methods: MSCs were treated with a gradient concentration of Osthole (6.25 µM, 12.5 µM, and 25 µM). Cell proliferation was assessed by western blotting with the proliferating cell nuclear antigen (PCNA) and Cyclin D1 antibodies, fluorescence activated cell sorting (FACS), and cell counting kit 8 (CCK8). MSCs were cultured in osteogenesis-induced medium for one or two weeks. The osteogenic differentiation of MSCs was estimated by Alkaline Phosphatase (ALP) staining, Alizarin red staining, Calcium influx, and quantitative PCR (qPCR). The underlying mechanism of Osthole-induced osteogenesis was further evaluated by western blotting with antibodies in Wnt/β-catenin, PI3K/Akt, BMPs/smad1/5/8, and MAPK signaling pathways. Results: Osthole inhibited proliferation of rat MSCs in a dose-dependent manner. Osthole suppressed osteogenic differentiation of rat MSCs by down-regulating the activities of Wnt/β-catenin and Erk1/2-MAPK signaling. Conclusions: Osthole inhibits the proliferation and osteogenic differentiation of rat MSCs, which might be mediated through blocking the Wnt/β-catenin and Erk1/2-MAPK signaling pathways.

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2,4,5-Trimethoxyldalbergiquinol promotes osteoblastic differentiation and mineralization via the BMP and Wnt/β-catenin pathway

Cited by 80 publications

References 40 publications

Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways

Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways

Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/β-Catenin and Erk1/2-MAPK Pathways

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