Recent Advances of Osterix Transcription Factor in Osteoblast Differentiation and Bone Formation

Liu, Qian; Li, Mao; Wang, Shiyi; Xiao, Zhousheng; Xiong, Yuanyuan; Wang, Guangwei

doi:10.3389/fcell.2020.601224

Cited by 118 publications

(91 citation statements)

References 139 publications

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“…The presence of rSp7 mRNA was greater in the implants loaded with BMP-2 and VEGF but did not differ between the MC and UC implants. Osterix is known to be one of the key transcription factors that regulate osteoblast differentiation and maturation [ 43 ]. Hence, its greater presence in the implants loaded with BMP-2 and VEGF indicates that there is still an active process of osteoblastic differentiation happening within these ectopic ossicles.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Pore Directionality of Collagen Scaffolds on Cell Differentiation and In Vivo Osteogenesis

et al. 2021

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Although many bone substitutes have been designed and produced, the development of bone tissue engineering products that mimic the microstructural characteristics of native bone remains challenging. It has been shown that pore orientation within collagen scaffolds influences bone matrix formation by the endochondral route. In addition, that the unidirectional orientation of the scaffolds can limit the growth of blood vessels. However, a comparison between the amount of bone that can be formed in scaffolds with different pore orientations in addition to analyzing the effect of loading osteogenic and proangiogenic factors is still required. In this work we fabricated uni- and multidirectional collagen sponges and evaluated their microstructural, physicochemical, mechanical and biological characteristics. Although the porosity and average pore size of the uni- and multidirectional scaffolds was similar (94.5% vs. 97.1% and 260 µm vs. 269 µm, respectively) the unidirectional sponges had a higher tensile strength, Young’s modulus and capacity to uptake liquids than the multidirectional ones (0.271 MPa vs. 0.478 MPa, 9.623 MPa vs. 3.426 MPa and 8000% mass gain vs. 4000%, respectively). Culturing of rat bone marrow mesenchymal stem cells demonstrated that these scaffolds support cell growth and osteoblastic differentiation in the presence of BMP-2 in vitro, although the pore orientation somehow affected cell attachment and differentiation. The evaluation of the ability of the scaffolds to support bone growth when loaded with BMP-2 or BMP-2 + VEGF in an ectopic rat model showed that they both supported bone formation. Histological analysis and quantification of mineralized matrix revealed that the pore orientation of the collagen scaffolds influenced the osteogenic process.

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Section: Discussionmentioning

confidence: 99%

The Effect of Pore Directionality of Collagen Scaffolds on Cell Differentiation and In Vivo Osteogenesis

et al. 2021

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“…Osterix (Osx or Sp7) is a zinc-finger family transcription factor required for osteoblast proliferation and differentiation [ 1 ]. It is expressed in early hypertrophic chondrocytes and inhibits chondrogenesis in favor of chondrocyte differentiation to regulate endochondral ossification [ 2 , 3 , 4 ]. Osterix-null embryos develop normal cartilage, but the osteoblasts fail to differentiate during endochondral ossification, resulting in a complete lack of bone tissue [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Skeletal Deformities in Osterix-Cre;Tgfbr2f/f Mice May Cause Postnatal Death

Corps

Stanwick

Rectenwald

et al. 2021

Genes

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Transforming growth factor β (TGFβ) signaling plays an important role in skeletal development. We previously demonstrated that the loss of TGFβ receptor II (Tgfbr2) in Osterix-Cre-expressing mesenchyme results in defects in bones and teeth due to reduced proliferation and differentiation in pre-osteoblasts and pre-odontoblasts. These Osterix-Cre;Tgfbr2f/f mice typically die within approximately four weeks for unknown reasons. To investigate the cause of death, we performed extensive pathological analysis on Osterix-Cre- (Cre-), Osterix-Cre+;Tgfbr2f/wt (HET), and Osterix-Cre+;Tgfbr2f/f (CKO) mice. We also crossed Osterix-Cre mice with the ROSA26mTmG reporter line to identify potential off-target Cre expression. The findings recapitulated published skeletal and tooth abnormalities and revealed previously unreported osteochondral dysplasia throughout both the appendicular and axial skeletons in the CKO mice, including the calvaria. Alterations to the nasal area and teeth suggest a potentially reduced capacity to sense and process food, while off-target Cre expression in the gastrointestinal tract may indicate an inability to absorb nutrients. Additionally, altered nasal passages and unexplained changes in diaphragmatic muscle support the possibility of hypoxia. We conclude that these mice likely died due to a combination of breathing difficulties, malnutrition, and starvation resulting primarily from skeletal deformities that decreased their ability to sense, gather, and process food.

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“…Interestingly, osteocalcin is one of the main components of ground substance that, together with Type 1 collagen, constitute the bone matrix (Hill et al, 2005;Asada et al, 2013;Fulzele et al, 2013). Osx demonstrates a multifunctional role on osteoblast differentiation, growth and homeostasis, since its deletion in several time points postnatally in growing and adult bones causes defects in maturation, morphology and function of osteocytes (Zhou et al, 2010;Liu et al, 2020). Decreased Oc expression may lend insight into a physiologic basis for the Tle4 knockoutinduced bone phenotype.…”

Section: Discussionmentioning

confidence: 99%

TLE4 Is a Critical Mediator of Osteoblast and Runx2-Dependent Bone Development

Shin

Theodorou

Holland

et al. 2021

Front. Cell Dev. Biol.

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Healthy bone homeostasis hinges upon a delicate balance and regulation of multiple processes that contribute to bone development and metabolism. While examining hematopoietic regulation by Tle4, we have uncovered a previously unappreciated role of Tle4 on bone calcification using a novel Tle4 null mouse model. Given the significance of osteoblasts in both hematopoiesis and bone development, this study investigated how loss of Tle4 affects osteoblast function. We used dynamic bone formation parameters and microCT to characterize the adverse effects of Tle4 loss on bone development. We further demonstrated loss of Tle4 impacts expression of several key osteoblastogenic genes, including Runx2, Oc, and Ap, pointing toward a potential novel mechanism for Tle4-dependent regulation of mammalian bone development in collaboration with the RUNX family members.

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Recent Advances of Osterix Transcription Factor in Osteoblast Differentiation and Bone Formation

Cited by 118 publications

References 139 publications

The Effect of Pore Directionality of Collagen Scaffolds on Cell Differentiation and In Vivo Osteogenesis

The Effect of Pore Directionality of Collagen Scaffolds on Cell Differentiation and In Vivo Osteogenesis

Skeletal Deformities in Osterix-Cre;Tgfbr2f/f Mice May Cause Postnatal Death

TLE4 Is a Critical Mediator of Osteoblast and Runx2-Dependent Bone Development

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