Identification of FGF2-Response Element in the Rat Bone Sialoprotein Gene Promoter

Shimizu-Sasaki, Emi; Yamazaki, Masahito; Furuyama, Shunsuke; Saito, Hiroshi; Sodek, Jaro; Ogata, Yorimasa

doi:10.1080/03008200390152179

Cited by 6 publications

(1 citation statement)

References 29 publications

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“…For example, in the absence of BSP, osteoclast differentiation is impaired, and murine models lacking OPN exhibit osteopetrosis 83,84 . Additionally, BSP KO mice exhibit root resorption and FGF2 has been reported to increase BSP transcription 85,86 . While speculative, infigratinib mediation of extracellular matrix proteins may be protective against root resorption by regulating osteoclastogenesis, further demonstrating the diversity of FGFR/FGF roles in mineralized tissue homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Infigratinib, a selective FGFR1‐3 tyrosine kinase inhibitor, alters dentoalveolar development at high doses

Michel

Aitken

Glover

et al. 2023

Developmental Dynamics

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BackgroundFibroblast growth factor receptor‐3 (FGFR3) gain‐of‐function mutations are linked to achondroplasia. Infigratinib, a FGFR1‐3 tyrosine kinase inhibitor, improves skeletal growth in an achondroplasia mouse model. FGFs and their receptors have critical roles in developing teeth, yet effects of infigratinib on tooth development have not been assessed. Dentoalveolar and craniofacial phenotype of Wistar rats dosed with low (0.1 mg/kg) and high (1.0 mg/kg) dose infigratinib were evaluated using micro‐computed tomography, histology, and immunohistochemistry.ResultsMandibular third molars were reduced in size and exhibited aberrant crown and root morphology in 100% of female rats and 80% of male rats at high doses. FGFR3 and FGF18 immunolocalization and extracellular matrix protein expression were unaffected, but cathepsin K (CTSK) was altered by infigratinib. Cranial vault bones exhibited alterations in dimension, volume, and density that were more pronounced in females. In both sexes, interfrontal sutures were significantly more patent with high dose vs vehicle.ConclusionsHigh dose infigratinib administered to rats during early stages affects dental and craniofacial development. Changes in CTSK from infigratinib in female rats suggest FGFR roles in bone homeostasis. While dental and craniofacial disruptions are not expected at therapeutic doses, our findings confirm the importance of dental monitoring in clinical studies.

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Section: Discussionmentioning

confidence: 99%

Infigratinib, a selective FGFR1‐3 tyrosine kinase inhibitor, alters dentoalveolar development at high doses

Michel

Aitken

Glover

et al. 2023

Developmental Dynamics

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Cyclic acetal hydroxyapatite composites and endogenous osteogenic gene expression of rat marrow stromal cells

Patel

Dunn

Tostanoski

et al. 2009

J Tissue Eng Regen Med

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In this study, bone marrow stromal cells (BMSCs) were differentiated on cyclic acetal composites containing hydroxyapatite (HA) particles (110 or 550 nm). These composites were evaluated for their role in influencing osteogenic signalling by encapsulated BMSCs. While a number of factors exert influence on osteogenic signalling during the production of an osteogenic matrix, we hypothesize that HA particles may upregulate bone growth factor expression due to enhanced BMSC adhesion. To this end, fluorescence-activated cell sorting (FACS) analysis was performed for the evaluation of BMSC surface marker expression after culture on two-dimensional (2D) cyclic acetal/HA composites. Three-dimensional (3D) composites were then fabricated by incorporating 110 or 550 nm HA particles at 5, 10 and 50 ng/ml concentrations. Bone growth factor molecules (TGFbeta1, FGF-2 and PDGFa), bone biomarker molecules (ALP, OC, OPN and OCN) and extracellular matrix-related molecules (FN, MMP-13, Dmp1 and aggrecan) were selected for evaluation of osteogenic signalling mechanisms when in presence of these composites. FACS results at day 0 demonstrated that BMSCs were a heterogeneous population with a small percentage of cells staining positive for CD29, CD90 and CD51/61, while staining negative for CD34 and CD45. At day 3, a significant enrichment of cells staining strongly for CD29, CD90 and CD51/61 was achieved. Gene expression patterns for bone growth factors and extracellular matrix molecules were found to be largely dependent upon the size of HA particles. Bone marker molecules, except OCN, had unaltered expression patterns in response to the varied size of HA particles. Overall, the results indicate that larger-sized HA particles upregulate PDGF and these groups were also associated with the most significant increase in osteodifferentiation markers, particularly ALP. Our results suggest that endogenous signalling is dependent upon material properties. Furthermore, we propose that studying gene expression patterns induced by the surrounding biomaterials environment is a fundamental step in the creation of engineered tissues.

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Osteoadherin is Upregulated by Mature Osteoblasts and Enhances Their In Vitro Differentiation and Mineralization

et al. 2008

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During the process of differentiation, osteoblasts commit through strictly controlled checkpoints under the influence of several growth factors, cytokines, and extracellular matrix (ECM) proteins. The mineralized tissue-specific ECM component osteoadherin (OSAD) belongs to the small leucine-rich repeat protein family of proteoglycans. Proteoglycans modulate cellular behavior either through the attached glycosaminoglycan chains or by direct protein-protein interactions via the core protein sequences. Leucine-rich repeats have been shown to directly interact with cell-surface receptors such as epidermal growth factor receptor, blocking its ability to bind its ligand. In the present study, we investigated the influence of OSAD on the behavior and maturation of MC3T3E1 osteoblasts. OSAD overexpression and repression clones were created by stably transfecting with plasmids coding for either mouse OSAD cDNA or small-hairpin RNA, targeted against mouse OSAD. Overexpression of OSAD resulted in an increase of osteoblast differentiation features, such as increased alkaline phosphatase (ALP) activity and increased in vitro mineralization, as well as reduced proliferation and migration. Bone sialoprotein (BSP) levels were unchanged, while upregulation of osteocalcin (OC) and osteoglycin (OGN) was observed. Conversely, repression of OSAD expression resulted in increased cell proliferation and migration. BSP and OC were unaffected, while OGN was downregulated. ALP activity was reduced, though no change in in vitro mineralization was observed. We conclude that OSAD overexpression enhanced the differentiation and maturation of osteoblasts in vitro.

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Identification of FGF2-Response Element in the Rat Bone Sialoprotein Gene Promoter

Cited by 6 publications

References 29 publications

Infigratinib, a selective FGFR1‐3 tyrosine kinase inhibitor, alters dentoalveolar development at high doses

Infigratinib, a selective FGFR1‐3 tyrosine kinase inhibitor, alters dentoalveolar development at high doses

Cyclic acetal hydroxyapatite composites and endogenous osteogenic gene expression of rat marrow stromal cells

Osteoadherin is Upregulated by Mature Osteoblasts and Enhances Their In Vitro Differentiation and Mineralization

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