Expression Profile of Osteoblast Lineage at Defined Stages of Differentiation

Kalajzić, Ivo; Staal, Ada; Yang, Wen-Pin; Wu, Yuli; Johnson, Susan E.; Feyen, Jean H.M.; Krueger, Winfried; Maye, Peter; Fang, Yu; Zhao, Yunmei; Kuo, Lynn; Gupta, Rishi; Achenie, Luke E.K.; Wang, Hsin-Wei; Shin, Dong-Guk; Rowe, David W.

doi:10.1074/jbc.m413834200

Cited by 155 publications

(146 citation statements)

References 29 publications

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“…The increase in osteoblast numbers and in bone mass would provide a negative-feedback signal to the progenitors, including the CFU-F, causing their inhibition to proliferate. In support of this, differentiated osteoblasts or osteocytes have been found to produce Wnt inhibitors such as DKK1, which is strongly upregulated during the late phases of osteoblast differentiation (22) and has been shown to inhibit activation of canonical Wnt signaling and osteoblast differentiation. (23) The presence of a feedback mechanism in vivo would explain the discrepancy between our in vivo and in vitro results.…”

Section: Discussionmentioning

confidence: 90%

Glycogen synthase kinase-3α/β inhibition promotes in vivo amplification of endogenous mesenchymal progenitors with osteogenic and adipogenic potential and their differentiation to the osteogenic lineage

Gambardella

Nagaraju

O’Shea

et al. 2010

Journal of Bone and Mineral Research

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Small molecules are attractive therapeutics to amplify and direct differentiation of stem cells. They also can be used to understand the regulation of their fate by interfering with specific signaling pathways. Mesenchymal stem cells (MSCs) have the potential to proliferate and differentiate into several cell types, including osteoblasts. Activation of canonical Wnt signaling by inhibition of glycogen synthase kinase 3 (GSK-3) has been shown to enhance bone mass, possibly by involving a number of mechanisms ranging from amplification of the mesenchymal stem cell pool to the commitment and differentiation of osteoblasts. Here we have used a highly specific novel inhibitor of GSK-3, AR28, capable of inducing b-catenin nuclear translocation and enhanced bone mass after 14 days of treatment in BALB/c mice. We have shown a temporally regulated increase in the number of colony-forming units-osteoblast (CFU-O) and -adipocyte (CFU-A) but not colony-forming units-fibroblast (CFU-F) in mice treated for 3 days. However, the number of CFU-O and CFU-A returned to normal levels after 14 days of treatment, and the number of CFU-F was decreased significantly. In contrast, the number of osteoblasts increased significantly only after 14 days of treatment, and this was seen together with a significant decrease in bone marrow adiposity. These data suggest that the increased bone mass is the result of an early temporal wave of amplification of a subpopulation of MSCs with both osteogenic and adipogenic potential, which is driven to osteoblast differentiation at the expense of adipogenesis. ß

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Section: Discussionmentioning

confidence: 90%

Glycogen synthase kinase-3α/β inhibition promotes in vivo amplification of endogenous mesenchymal progenitors with osteogenic and adipogenic potential and their differentiation to the osteogenic lineage

Gambardella

Nagaraju

O’Shea

et al. 2010

Journal of Bone and Mineral Research

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“…Materials that promote osteoblastic differentiation upregulate osteospecific genes 28 resulting in the neogenesis of mineralized matrix, bony tissue formation, and deposition. The manipulation of a substrate's topography to affect its adhesive potential and the ability of cells to adhere at the cell-substrate interface may be viewed as an approach to direct and organize the adhesion and differentiation of migrating cells in bone repair.…”

Section: Discussionmentioning

confidence: 99%

Regulation of implant surface cell adhesion: characterization and quantification of S‐phase primary osteoblast adhesions on biomimetic nanoscale substrates

Biggs

Richards

Gadegaard

et al. 2006

Journal Orthopaedic Research

109

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Integration of an orthopedic prosthesis for bone repair must be associated with osseointegration and implant fixation, an ideal that can be approached via topographical modification of the implant/bone interface. It is thought that osteoblasts use cellular extensions to gather spatial information of the topographical surroundings prior to adhesion formation and cellular flattening. Focal adhesions (FAs) are dynamic structures associated with the actin cytoskeleton that form adhesion plaques of clustered integrin receptors that function in coupling the cell cytoskeleton to the extracellular matrix (ECM). FAs contain structural and signalling molecules crucial to cell adhesion and survival. To investigate the effects of ordered nanotopographies on osteoblast adhesion formation, primary human osteoblasts (HOBs) were cultured on experimental substrates possessing a defined array of nanoscale pits. Nickel shims of controlled nanopit dimension and configuration were fabricated by electron beam lithography and transferred to polycarbonate (PC) discs via injection molding. Nanopits measuring 120 nm diameter and 100 nm in depth with 300 nm center-center spacing were fabricated in three unique geometric conformations: square, hexagonal, and near-square (300 nm spaced pits in square pattern, but with AE50 nm disorder). Immunofluorescent labeling of vinculin allowed HOB adhesion complexes to be visualized and quantified by image software. Perhipheral adhesions as well as those within the perinuclear region were observed, and adhesion length and number were seen to vary on nanopit substrates relative to smooth PC. S-phase cells on experimental substrates were identified with bromodeoxyuridine (BrdU) immunofluorescent detection, allowing adhesion quantification to be conducted on a uniform flattened population of cells within the S-phase of the cell cycle. Findings of this study demonstrate the disruptive effects of ordered nanopits on adhesion formation and the role the conformation of nanofeatures plays in modulating these effects. Highly ordered arrays of nanopits resulted in decreased adhesion formation and a reduction in adhesion length, while introducing a degree of controlled disorder present in near-square arrays, was shown to increase focal adhesion formation and size. HOBs were also shown to be affected morphologicaly by the presence and conformation of nanopits. Ordered arrays affected cellular spreading, and induced an elongated cellular phenotype, indicative of increased motility, while near-square nanopit symmetries induced HOB spreading. It is postulated that nanopits affect osteoblast-substrate adhesion by directly or indirectly affecting adhesion complex formation, a phenomenon dependent on nanopit dimension and conformation. ß

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“…Osteoblast differentiation is stimulated by some hormones and local factors which act on signalling pathways in cells within the osteoprogenitor lineage (15) . Various pathways such as BMP, transforming growth factor-b, insulin-like growth factor, fibroblast growth factor, Hedgehog, WNT (wingless-type MMTV integration site family) and mitogen-activated protein kinase (MAPK) have been implicated (15 -19) (Fig.…”

Section: Regulation Of Osteoblastogenesismentioning

confidence: 99%

When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols

2009

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Recent research has provided insights into dietary components that may optimise bone health and stimulate bone formation. Fruit and vegetable intake, as well as grains and other plant-derived food, have been linked to decreased risk of major chronic diseases including osteoporosis. This effect has been partially attributed to the polyphenols found in these foods. Thus, it has been suggested that these compounds may provide desirable bone health benefits through an action on bone cell metabolism. The present review will focus on how some polyphenols can modulate osteoblast function and reports which cellular signalling pathways are potentially implicated. However, to date, despite numerous investigations, few studies have provided clear evidence that phenolic compounds can act on osteoblasts. Polyphenols cited in the present review seem to be able to modulate the expression of transcription factors such as runt-related transcription factor-2 (Runx2) and Osterix, NF-κB and activator protein-1 (AP-1). It appears that polyphenols may act on cellular signalling such as mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP), oestrogen receptor and osteoprotegerin/receptor activator of NF-κB ligand (OPG/RANKL) and thus may affect osteoblast functions. However, it is also important to take in account the possible interaction of these compounds on osteoclast metabolism to better understand the positive correlation reported between the consumption of fruit and vegetables and bone mass.

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Expression Profile of Osteoblast Lineage at Defined Stages of Differentiation

Cited by 155 publications

References 29 publications

Glycogen synthase kinase-3α/β inhibition promotes in vivo amplification of endogenous mesenchymal progenitors with osteogenic and adipogenic potential and their differentiation to the osteogenic lineage

Glycogen synthase kinase-3α/β inhibition promotes in vivo amplification of endogenous mesenchymal progenitors with osteogenic and adipogenic potential and their differentiation to the osteogenic lineage

Regulation of implant surface cell adhesion: characterization and quantification of S‐phase primary osteoblast adhesions on biomimetic nanoscale substrates

When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols

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