A Fundamental Transcription Factor for Bone and Cartilage

Komori, Toshihisa

doi:10.1006/bbrc.2000.3460

Cited by 53 publications

(35 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Enhanced mineralization was noted on rougher surfaces relative to the grooved implant surface and the tissue culture plates. 35 The transcription factor, Runx2 (Core binding factor a1, Cbfa1), plays an essential role in steering multipotent mesenchymal precursor cells toward an osteoblastic lineage, 36 and Runx2 regulates osteoblast differentiation. 37 Aside from the direct effects on the cytoskeleton, integrin-mediated signaling pathways are also known to affect gene expression, and increased Cbfa1 gene expression has been noted on rougher surfaces.…”

Section: Discussionmentioning

confidence: 99%

Microrough titanium surface affects biologic response in MG63 osteoblast‐like cells

Kim¹,

Kim²,

Lim³

et al. 2006

J Biomedical Materials Res

118

View full text Add to dashboard Cite

The purpose of this study was to define the surface properties of prepared titanium (Ti) disks, which served as a model system, and to contrast the biologic response of MG63 cells exposed to Ti disks with different levels of surface roughness. The surface properties interact with each other, resulting in a change of other surface qualities in addition to roughness due to the surface roughening procedure. The machined Ti disks were roughened by sandblasting and electric glow discharging. The surface properties of the Ti specimens were inspected through a comprehensive surface analysis. MG63 cell behaviors were compared along with cell number, alkaline phosphatase (ALP) activity, Runx2 gene expression, and type I collagen production. Statistics were evaluated, using analysis of variance (ANOVA). The sandblasted Ti disks demonstrated well-controlled surface roughness features and meaningful average roughness ranges, including the surface roughness of the "modern" microrough implant, used clinically. With increasing Ti surface roughness, the cell number decreased, while the ALP activity, type I collagen production, and Runx2 gene expression increased significantly. The rougher the Ti surface was, the sooner the Runx2 gene was expressed. Based on these results, we suggest that the microrough Ti surfaces of the 1-3 mum range may contribute effectively to osteogenic differentiation and proliferation in MG63 cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Microrough titanium surface affects biologic response in MG63 osteoblast‐like cells

Kim¹,

Kim²,

Lim³

et al. 2006

J Biomedical Materials Res

118

View full text Add to dashboard Cite

show abstract

“…Development of osteoblasts from mesenchymal cells depends on Runx2 (formerly Cbfa1); no ossification occurs without its activity (Ducy et al, 1997;Komori et al, 1997;Otto et al, 1997;Komori, 2000;Yamaguchi et al, 2000). RUNX2 protein regulates several bone-specific genes, such as bone sialoproteins [BSPI (also known as Spp1, Opn and osteopontinMouse Genome Informatics) and BspII], collagen type I and osteocalcin (also known as Bglap1 -Mouse Genome Informatics) (Ducy et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Regulation of skeletogenic differentiation in cranial dermal bone

et al. 2007

View full text Add to dashboard Cite

Although endochondral ossification of the limb and axial skeleton is relatively well-understood, the development of dermal (intramembranous) bone featured by many craniofacial skeletal elements is not nearly as well-characterized. We analyzed the expression domains of a number of markers that have previously been associated with endochondral skeleton development to define the cellular transitions involved in the dermal ossification process in both chick and mouse. This led to the recognition of a series of distinct steps in the dermal differentiation pathways, including a unique cell type characterized by the expression of both osteogenic and chondrogenic markers. Several signaling molecules previously implicated in endochondrial development were found to be expressed during specific stages of dermal bone formation. Three of these were studied functionally using retroviral misexpression. We found that activity of bone morphogenic proteins (BMPs) is required for neural crest-derived mesenchyme to commit to the osteogenic pathway and that both Indian hedgehog (IHH) and parathyroid hormone-related protein (PTHrP, PTHLH) negatively regulate the transition from preosteoblastic progenitors to osteoblasts. These results provide a framework for understanding dermal bone development with an aim of bringing it closer to the molecular and cellular resolution available for the endochondral bone development.

show abstract

“…Runx2 levels increase greatly during osteoblast differentiation, whereas homozygous gene deletion of Runx2 limits bone formation, and few, if any, differentiated osteoblasts are found in Runx2-deficient mice (7). Importantly, the Runt domain contains sequences essential for DNA binding, and this region seems to be required for heterodimerization with several other nuclear transcription factors.…”

mentioning

confidence: 99%

“…Although in some instances glucocorticoid may enhance Runx2 mRNA expression, in vitro glucocorticoid in excess rapidly depletes the amount of functional Runx2 nuclear protein, with an accompanying inhibitory effect on Runx2-dependent gene expression (19,20). This seems to reprise the downstream events that occur with glucocorticoid therapy or with Runx2 gene deletion in vivo (7) and would essentially limit osteoblast activity in the adult remodeling skeleton. Bone loss also occurs after menopause or with sex steroid depletion.…”

mentioning

confidence: 99%

Runx2 Integrates Estrogen Activity in Osteoblasts

McCarthy

Chang

Liu

et al. 2003

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

Steroids significantly effect skeletal integrity. For example, bone mass decreases with glucocorticoid excess or with estrogen depletion after menopause. Glucocorticoid suppresses gene expression by an essential skeletal tissue transcription factor, Runx2, in rat osteoblasts. We now report that estrogen enhances Runx2 activity in dose-and estrogen receptor-dependent ways independently of changes in Runx2 levels or its DNA binding potential. Estrogen receptor and Runx2 can be collected by co-immunoprecipitation. By two-hybrid gene expression analysis, high affinity complex formation involves portions of Runx2 outside of its own DNA binding domain and the DNA binding domain of the estrogen receptor. Consistent with this interaction, the stimulatory effect of estrogen on Runx2 activity is lost when the DNA binding domain of the estrogen receptor is eliminated. Unlike the stimulatory effect of estrogen and the inhibitory effect of glucocorticoid, androgen fails to increase Runx2 activity, whereas Runx2 potently suppresses gene expression induced by all three steroids. Finally, estrogen increases gene transcription by the transforming growth factor-␤ type I receptor gene promoter, which contains several Runx binding sequences, and enhances Smad dependent gene expression by transforming growth factor-␤ in osteoblasts. These results reveal that Runx2 can integrate complex effects on gene transcription in hormone-, growth factor-, and tissue-restricted ways.

show abstract

A Fundamental Transcription Factor for Bone and Cartilage

Cited by 53 publications

References 45 publications

Microrough titanium surface affects biologic response in MG63 osteoblast‐like cells

Microrough titanium surface affects biologic response in MG63 osteoblast‐like cells

Regulation of skeletogenic differentiation in cranial dermal bone

Runx2 Integrates Estrogen Activity in Osteoblasts

Contact Info

Product

Resources

About