Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in vitro

Gordon, Jonathan A. R.; Tye, Coralee E.; Sampaio, Arthur V.; Underhill, T. Michael; Hunter, Graeme; Goldberg, Harvey A.

doi:10.1016/j.bone.2007.04.191

Cited by 292 publications

(216 citation statements)

References 51 publications

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“…The osteoblasts derived from ALP-deficient mice are unable to form mineralized nodules (34). Increased ALP activity is closely associated with osteoblastic differentiation (35). We have observed upregulation of ALP expression in osteosarcoma cells with Coleusin factor treatment in a dose¼dependent manner, and ALP activity is also significantly elevated (Fig.…”

Section: Discussionmentioning

confidence: 74%

Coleusin Factor, a Novel Anticancer Diterpenoid, Inhibits Osteosarcoma Growth by Inducing Bone Morphogenetic Protein-2–Dependent Differentiation

Geng

Sun

et al. 2014

Molecular Cancer Therapeutics

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Coleusin factor is a diterpenoid compound isolated from the root of a tropical plant, Coleus forskohlii. Although Coleusin factor has been reported to suppress proliferation of and induce apoptosis in several types of cancer cells, the effects of Coleusin factor on osteosarcoma and the underlying mechanism are still not fully understood. In this study, we show that Coleusin factor treatment potently inhibits the growth of osteosarcoma cells associated with G 1 cell-cycle arrest. Interestingly, apoptosis and cell death are not induced. Instead, Coleusin factor causes osteosarcoma cells to exhibit typical properties of differentiated osteoblasts, including a morphologic alteration resembling osteoblasts, the expression of osteoblast differentiation markers, elevated alkaline phosphatase activity, and increased cellular mineralization. Coleusin factor treatment significantly increases the expression of bone morphogenetic protein-2 (BMP-2), a crucial osteogenic regulator, and runt-related transcription factor 2 (RUNX2), one of the key transcription factors of the BMP pathway. When BMP-2 signaling is blocked, Coleusin factor fails to inhibit cell proliferation and to induce osteoblast differentiation. Thus, upregulation of BMP-2 autocrine is critical for Coleusin factor to induce osteoblast differentiation and exert its anticancer effects on osteosarcoma. Importantly, administration of Coleusin factor inhibits the growth of osteosarcoma xenografted in nude mice without systemic or immunologic toxicity. Osteosarcoma is a highly aggressive cancer marked by the loss of normal differentiation. Coleusin factor represents a new type of BMP-2 inducer that restores differentiation in osteosarcoma cells. It may provide a promising therapeutic strategy against osteosarcoma with minimal side effects. Mol Cancer Ther; 13(6);

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Section: Discussionmentioning

confidence: 74%

Coleusin Factor, a Novel Anticancer Diterpenoid, Inhibits Osteosarcoma Growth by Inducing Bone Morphogenetic Protein-2–Dependent Differentiation

Geng

Sun

et al. 2014

Molecular Cancer Therapeutics

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“…This would therefore infer that the stimulatory effects of exogenously added HTRA1 protein on hBMSC osteogenesis and mineralization of differentiating bone-forming cells may be reliant on its ability to regulate factors present within the actively mineralizing ECM. In addition to its ability to affect ECM mineral content, HTRA1 also induced a significant upregulation in the expression of several positive regulators of mineralization, including BMP5 and IBSP [30,31], although a large proportion of well-known osteogenic genes such as RUNX2, ALP, and SPP1 remained unaffected. In addition, the expression level of a potent negative-regulator of mineral formation, SOST [32, 33], was markedly downregulated in hBMSCs treated with HTRA1 and may thus represent an additional mechanism by which mineral deposition is enhanced in differentiating bone-forming cells.…”

Section: Discussionmentioning

confidence: 99%

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

et al. 2012

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Mammalian high-temperature requirement serine protease A1 (HTRA1) is a secreted member of the trypsin family of serine proteases which can degrade a variety of bone matrix proteins and as such has been implicated in musculoskeletal development. In this study, we have investigated the role of HTRA1 in mesenchymal stem cell (MSC) osteogenesis and suggest a potential mechanism through which it controls matrix mineralization by differentiating boneforming cells. Osteogenic induction resulted in a significant elevation in the expression and secretion of HTRA1 in MSCs isolated from human bone marrow-derived MSCs (hBMSCs), mouse adipose-derived stromal cells (mASCs), and mouse embryonic stem cells. Recombinant HTRA1 enhanced the osteogenesis of hBMSCs as evidenced by significant changes in several osteogenic markers including integrin-binding sialoprotein (IBSP), bone morphogenetic protein 5 (BMP5), and sclerostin, and promoted matrix mineralization in differentiating boneforming osteoblasts. These stimulatory effects were not observed with proteolytically inactive HTRA1 and were abolished by small interfering RNA against HTRA1. Moreover, loss of HTRA1 function resulted in enhanced adipogenesis of hBMSCs. HTRA1 Immunofluorescence studies showed colocalization of HTRA1 with IBSP protein in osteogenic mASC spheroid cultures and was confirmed as being a newly identified HTRA1 substrate in cell cultures and in proteolytic enzyme assays. A role for HTRA1 in bone regeneration in vivo was also alluded to in bone fracture repair studies where HTRA1 was found localized predominantly to areas of new bone formation in association with IBSP. These data therefore implicate HTRA1 as having a central role in osteogenesis through modification of proteins within the extracellular matrix. STEM CELLS

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“…2C and 2D). Runx2 is the most important transcription factor for the osteogenic differentiation and controls the expression of bone forming genes in osteoblasts (Komori et al, 1997;Xiao et al, 2000;Gordon et al, 2007). So we detected whether VC could induce the expression of Runx2.…”

Section: Vc Induced the Osteogenic Differentiation Of Pdl Progenitor mentioning

confidence: 94%

Vitamin C induces periodontal ligament progenitor cell differentiation via activation of ERK pathway mediated by PELP1

et al. 2013

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The differentiation of periodontal ligament (PDL) progenitor cells is important for maintaining the homeostasis of PDL tissue and alveolar bone. Vitamin C (VC), a water-soluble nutrient that cannot be biosynthesized by humans, is vital for mesenchymal stem cells differentiation and plays an important role in bone remodeling. Therefore, the objective of this study was to determine the function and mechanism of VC in PDL progenitor cells osteogenic differentiation at the molecular level. We demonstrated that VC could induce the osteogenic differentiation and maturation of PDL progenitor cell without other osteogenic agents. During the process, VC preferentially activated ERK1/2 but did not affect JNK or p38. Co-treatment with ERK inhibitor effectively decreased the Vitamin C-induced expression of Runx2. ERK inhibitor also abrogated Vitamin C-induced the minimized nodules formation. PELP1, a nuclear receptor co-regulator, was up-regulated under VC treatment. PELP1 knockdown inhibited ERK phosphorylation. The overexpression of PELP1 had a positive relationship with Runx2 expression. Taken together, we could make a conclude that VC induces the osteogenic differentiation of PDL progenitor cells via PELP1-ERK axis. Our fi nding implies that VC may have a potential in the regeneration medicine and application to periodontitis treatment.

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Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in vitro

Cited by 292 publications

References 51 publications

Coleusin Factor, a Novel Anticancer Diterpenoid, Inhibits Osteosarcoma Growth by Inducing Bone Morphogenetic Protein-2–Dependent Differentiation

Coleusin Factor, a Novel Anticancer Diterpenoid, Inhibits Osteosarcoma Growth by Inducing Bone Morphogenetic Protein-2–Dependent Differentiation

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

Vitamin C induces periodontal ligament progenitor cell differentiation via activation of ERK pathway mediated by PELP1

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