Wedelolactone Enhances Osteoblastogenesis through ERK- and JNK-mediated BMP2 Expression and Smad/1/5/8 Phosphorylation

Zhu, Duzhang; Deng, Xinyi; Han, Xiaofei; Sun, Xiao Xin; Pan, Taowen; Zheng, Liqin; Li, Yanqiu

doi:10.3390/molecules23030561

Cited by 26 publications

(22 citation statements)

References 38 publications

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“…Activation of the ERK/β‐catenin signalling pathway facilitates the osteogenic differentiation of BMSCs in vitro . In addition, Erk‐mediated phosphorylation of Smad promotes the osteogenic differentiation of BMSCs . In the current study, we showed that unOc promoted osteogenic differentiation of BMSCs via the Erk‐Smad/β‐catenin pathways, as evidenced by increased ALP activity, COLI production, calcified nodule formation, and expression of specific osteogenic genes including Osx, Runx2, ALP, and COLI.…”

Section: Discussionsupporting

confidence: 54%

Uncarboxylated osteocalcin promotes osteogenic differentiation of mouse bone marrow–derived mesenchymal stem cells by activating the Erk‐Smad/β‐catenin signalling pathways

Liu

Yang

2019

Cell Biochemistry & Function

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Uncarboxylated osteocalcin (unOc) is an osteoblast-derived hormone with multiple regulatory functions. Osteocalcin knockdown delays the maturation of mineral species and downregulates the expression of osteogenic-specific genes in human mesenchymal stromal cells. However, the underlying mechanisms remain unclear. Here, we investigated the effects of unOc on the osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) and discovered that unOc promoted osteogenic differentiation of BMSCs, which was characterized by increases in alkaline phosphatase (ALP) activity, type I collagen (COLI) production, calcified nodule formation, and expression of osteogenic-specific genes including the osterix, runtrelated transcription factor 2 (Runx2), ALP, and COLI genes. Further experiments indicated that unOc promoted the osteogenic differentiation of BMSCs via activation of the Erk-Smad/β-catenin signalling pathways. Significance of the study:Osteoporosis is associated with the osteogenic differentiation of BMSCs. In recent years, the role of unOc function as an endocrine hormone has received much attention. In this study, we reported for the first time that unOc promoted the osteogenic differentiation of mouse BMSCs through Erk-Smad/βcatenin signalling pathway. Our results highlight the importance of unOc as a hormone in promoting the osteogenic differentiation of BMSCs, indicating that this hormone may be beneficial in treatments for osteoporosis and fracture healing. KEYWORDSbone marrow-derived mesenchymal stem cells, Erk-Smad/β-catenin, osteogenic differentiation, signalling pathway, uncarboxylated osteocalcin

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Section: Discussionsupporting

confidence: 54%

Uncarboxylated osteocalcin promotes osteogenic differentiation of mouse bone marrow–derived mesenchymal stem cells by activating the Erk‐Smad/β‐catenin signalling pathways

Liu

Yang

2019

Cell Biochemistry & Function

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“…These MAPKs are the best-characterized downstream signaling pathways of the matrix microenvironment-integrin interactions in osteogenic cell types [44][45][46]. Consistent with the current results, MAPKs have been frequently reported as a key player for the osteogenic differentiation of various types of stem cells [47][48][49]. Regarding previous studies and our findings, these integrin-MAPK stepwise processes trigger the osteogenic induction of ESCs in response to the PDA/GO culture substrate.…”

Section: Discussionsupporting

confidence: 92%

Performance of the Polydopamine-Graphene Oxide Composite Substrate in the Osteogenic Differentiation of Mouse Embryonic Stem Cells

Shim¹,

Heo²

2021

IJMS

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Graphene oxide (GO) is a biocompatible material considered a favorable stem cell culture substrate. In this study, GO was modified with polydopamine (PDA) to facilitate depositing GO onto a tissue culture polystyrene (PT) surface, and the osteogenic performance of the PDA/GO composite in pluripotent embryonic stem cells (ESCs) was investigated. The surface chemistry of the PDA/GO-coated PT surface was analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A high cell viability of ESCs cultured on the PDA/GO composite-coated surface was initially ensured. Then, the osteogenic differentiation of the ESCs in response to the PDA/GO substrate was assessed by alkaline phosphatase (ALP) activity, intracellular calcium levels, matrix mineralization assay, and evaluation of the mRNA and protein levels of osteogenic factors. The culture of ESCs on the PDA/GO substrate presented higher osteogenic potency than that on the uncoated control surface. ESCs cultured on the PDA/GO substrate expressed significantly higher levels of integrin α5 and β1, as well as bone morphogenetic protein receptor (BMPR) types I and II, compared with the control groups. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38, and c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) was observed in ESCs culture on the PDA/GO substrate. Moreover, BMP signal transduction by SMAD1/5/8 phosphorylation was increased more in cells on PDA/GO than in the control. The nuclear translocation of SMAD1/5/8 in cells was also processed in response to the PDA/GO substrate. Blocking activation of the integrin α5/β1, MAPK, or SMAD signaling pathways downregulated the PDA/GO-induced osteogenic differentiation of ESCs. These results suggest that the PDA/GO composite stimulates the osteogenic differentiation of ESCs via the integrin α5/β1, MAPK, and BMPR/SMAD signaling pathways.

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“…Increased expression of BMP2 mRNA and Smad1/5/8 phosphorylation was blocked by SP600125 and PD98059, but not by SB203580. Our findings confirmed that wedelolactone enhanced osteoblastogenesis through induction of the JNK-and ERK-mediated BMP2-Smad1/5/8 pathway [54].…”

Section: Chinese Herbal Drugs That Enhance Osteoblastogenesis And/or supporting

confidence: 85%

Traditional Chinese Medicine Therapy for Targeting Osteoblastogenesis

Li¹

2019

Osteogenesis and Bone Regeneration

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Osteoblasts are derived from bone marrow mesenchymal stem cell (BMSC) precursors, which differentiate into mature osteoblasts and mediate bone formation. This process is called osteoblastogenesis. A deficiency in osteoblastogenesis of BMSCs can result in bone-related diseases including osteoporosis. Thus, developing drugs for targeting osteoblastogenesis from BMSCs has become one of the therapeutic strategies for osteoporosis. In China, kidney-nourishing Chinese herbal drugs such as ER-Zhi-Wan have been believed to be potential for treating osteoporosis through targeting osteoblast proliferation and differentiation. The key pathways for regulating osteoblastogenesis include canonical and noncanonical Wnt pathway, semaphorin-mediated pathway, and MAPK-mediated BMP2-Smad pathway. Some natural products have been confirmed to regulate more than one pathway and exert multi-target effect through the use of one compound or combined use of more than two compounds, such as wedelolactone and oleonuezhenide. In addition, tissue engineering provides a promising strategy in the field for targeting osteoblastogenesis. New types of biomaterials including hydroxyapatite (HAp) combined with Chinese medicine can exert enhanced effect on osteoblastogenesis and provide new therapy for treating osteoporosis.

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Wedelolactone Enhances Osteoblastogenesis through ERK- and JNK-mediated BMP2 Expression and Smad/1/5/8 Phosphorylation

Cited by 26 publications

References 38 publications

Uncarboxylated osteocalcin promotes osteogenic differentiation of mouse bone marrow–derived mesenchymal stem cells by activating the Erk‐Smad/β‐catenin signalling pathways

Uncarboxylated osteocalcin promotes osteogenic differentiation of mouse bone marrow–derived mesenchymal stem cells by activating the Erk‐Smad/β‐catenin signalling pathways

Performance of the Polydopamine-Graphene Oxide Composite Substrate in the Osteogenic Differentiation of Mouse Embryonic Stem Cells

Traditional Chinese Medicine Therapy for Targeting Osteoblastogenesis

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