A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner

Ohba, Shinsuke; Nakajima, Keiji; Komiyama, Yusuke; Kugimiya, Fumitaka; Igawa, Kazuyo; Itaka, Keiji; Moro, Toru; Nakamura, Kozo; Kawaguchi, Hiroshi; Takato, Tsuyoshi; Chung, Ung Il

doi:10.1016/j.bbrc.2007.03.173

Cited by 42 publications

(25 citation statements)

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“…Moreover, it also indicated that SAG alone might not be sufficient to direct the differentiation of these precursors into mature osteoblasts. In terms of molecules inducing osteoblast maturation, we identified the helioxanthin-derivative 4-(4-methoxyphenyl)pyrido[4′,3′:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH) as an osteogenic small molecule that acts on preosteoblasts in a bone morphogenetic protein (BMP)-dependent manner (Ohba et al., 2007b). Furthermore, we recently reported the combinatorial effect of SAG and TH on the differentiation of mesenchymal cells into osteoblasts (Maeda et al., 2013).…”

Section: Introductionmentioning

confidence: 99%

Stepwise Differentiation of Pluripotent Stem Cells into Osteoblasts Using Four Small Molecules under Serum-free and Feeder-free Conditions

Kanke¹,

Hara²,

Saito³

et al. 2014

Stem Cell Reports

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SummaryPluripotent stem cells are a promising tool for mechanistic studies of tissue development, drug screening, and cell-based therapies. Here, we report an effective and mass-producing strategy for the stepwise differentiation of mouse embryonic stem cells (mESCs) and mouse and human induced pluripotent stem cells (miPSCs and hiPSCs, respectively) into osteoblasts using four small molecules (CHIR99021 [CHIR], cyclopamine [Cyc], smoothened agonist [SAG], and a helioxanthin-derivative 4-(4-methoxyphenyl)pyrido[4′,3′:4,5]thieno[2,3-b]pyridine-2-carboxamide [TH]) under serum-free and feeder-free conditions. The strategy, which consists of mesoderm induction, osteoblast induction, and osteoblast maturation phases, significantly induced expressions of osteoblast-related genes and proteins in mESCs, miPSCs, and hiPSCs. In addition, when mESCs defective in runt-related transcription factor 2 (Runx2), a master regulator of osteogenesis, were cultured by the strategy, they molecularly recapitulated osteoblast phenotypes of Runx2 null mice. The present strategy will be a platform for biological and pathological studies of osteoblast development, screening of bone-augmentation drugs, and skeletal regeneration.

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Section: Introductionmentioning

confidence: 99%

Stepwise Differentiation of Pluripotent Stem Cells into Osteoblasts Using Four Small Molecules under Serum-free and Feeder-free Conditions

Kanke¹,

Hara²,

Saito³

et al. 2014

Stem Cell Reports

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“…The thieno [2,3-b]pyridine derivatives occupy special place and have attracted considerable attention because of their broad pharmacological activities, including anticancer [1][2][3][4][5][6][7][8][9], antiviral [10][11][12][13], anti-inflammatory [14][15][16][17], antimicrobial [18,19], antidiabetic [20][21][22][23], antihypertensive [24][25][26] and osteogenic [27,28] activities, in addition to treatment of CNS disorders [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Utility of thieno[2,3-b] pyridine derivatives in the synthesis of some condensed heterocyclic compounds with expected biological activity

Hassan¹,

Sarg²,

Said³

et al. 2013

Univers Org Chem

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“…The process of bone growth, regeneration, and remodeling is mediated in part by the immediate cell matrix environment (22). Ohba et al (23) suggested two possible mechanisms for the involvement of BMP signaling in the effects of icariin. First, icariin may indirectly activate BMP signaling through extracellular BMPs.…”

Section: Discussionmentioning

confidence: 99%

Icariin stimulates MC3T3-E1 cell proliferation and differentiation through up-regulation of bone morphogenetic protein-2

Zhang

2011

Int J Mol Med

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Abstract. Previous studies suggest that icariin has anabolic effects on bone, but the mechanisms are unknown. We aimed to investigate the osteogenic effects of icariin in an undifferentiated osteoblast cell line by detecting cell morphology, viability, cell cycling and bone morphogenetic protein-2 (BMP-2) expression. We treated pre-osteoblastic MC3T3-E1 cells with different concentrations of icariin [0 (as a control), 10, 20 and 40 ng/ml] for 48, 72 and 96 h. Cell morphology, viability and the cell cycle were examined and measured using microscopy, the MTT assay or flow cytometry, respectively. BMP-2-positive cells and BMP-2 protein expression levels in icariin-treated MC3T3-E1 cells were examined using immunohistochemistry staining with fluorescence optical density analysis and Western blotting. MC3T3-E1 cells showed typical characteristics of osteoblasts in response to treatment with icariin. Cells treated with all concentrations of icariin had increased percentages of S-phase cells and decreased percentages of G1-phase cells, especially in the 10 and 20 ng/ml icariin groups. The number of BMP-2-positive cells and BMP-2 protein expression levels in the 10 and 20 ng/ml icariin treatment groups were greater compared to the 0 and 40 ng/ml groups. Treatment of icariin promotes osteoblast MC3T3-E1 proliferation and differentiation in vitro, potentially owing to its role in increasing BMP-2 protein expression. Icariin potentially can be used as a drug in clinical settings to treat osteoporosis. IntroductionOsteoporosis is a serious public health issue and one of the most important aging-associated diseases, affecting millions of people (1,2). It is a silent disease that is defined as 'a skeletal disorder characterized by compromised bone strength, predisposing to an increased risk of fracture' (3). Bone strength reflects the interaction of two main characteristics: bone density and bone quality (4,5). Osteoporosis is characterized by the reduction of bone mass and disorganization of the trabecular architecture, resulting in weakening of the bone.For postmenopausal women, Epimedium pubescens flavonoids exert a beneficial effect on preventing bone loss (6). Epimedium-derived phytoestrogenic flavonoids can inhibit bone resorption, stimulate bone formation, and prevent ovariectomyinduced osteoporosis, all without resulting in uterine hyperplasia. Peng et al (7) suggested Epimedium-derived flavonoids had an anabolic effect on osteoporotic bone by concomitantly promoting the osteogenic differentiation of bone marrow stromal cells while suppressing adipogenic differentiation.Icariin, one of the primary active ingredients of Epimedium, reportedly has a potential anabolic effect on the bone (Fig. 1). It can stimulate the proliferation of rat bone marrow stromal cells, increase the number of colony-forming units of fibroblasts that stain positive for alkaline phosphatase and enhance alkaline phosphatase activity, osteocalcin secretion, and calcium deposition levels in a dose-dependent manner (8). Zhao et al (9) showed that i...

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A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner

Cited by 42 publications

References 25 publications

Stepwise Differentiation of Pluripotent Stem Cells into Osteoblasts Using Four Small Molecules under Serum-free and Feeder-free Conditions

Stepwise Differentiation of Pluripotent Stem Cells into Osteoblasts Using Four Small Molecules under Serum-free and Feeder-free Conditions

Utility of thieno[2,3-b] pyridine derivatives in the synthesis of some condensed heterocyclic compounds with expected biological activity

Icariin stimulates MC3T3-E1 cell proliferation and differentiation through up-regulation of bone morphogenetic protein-2

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