The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression

Park, Su Jin; Jung, Seung Hyun; Gadi, Jogeswar; Ryoo, Hyun‐Mo; Yook, Jong In; Choi, Han Seok; Rhee, Yumie; Kim, Cheol‐Hee; Lim, Sung Kil

doi:10.1016/j.bone.2010.02.027

Cited by 27 publications

(24 citation statements)

References 38 publications

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“…Zebrafish were previously shown to be a common and useful model for studying vertebrate development and gene function (23). Morpholino-targeted disruption of Sox11 in zebrafish further supported our in vitro data of the role of Sox11 in osteogenesis.…”

Section: Discussionsupporting

confidence: 80%

“…After sequencing, the fragments were sub cloned into pGL3-promoter vectors after digestion with the restriction enzymes KpnI/BglII. The Runx2 promoter construct used in this study was previously described by our group (23). Point mutations at putative Sox11 binding sites were introduced with an Expand Long Range dNTPack kit (Roche Applied Science, Mannheim, Germany) and point mutations were confirmed by DNA sequencing before analyzing reporter activity.…”

Section: Methodsmentioning

confidence: 99%

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The Transcription Factor Protein Sox11 Enhances Early Osteoblast Differentiation by Facilitating Proliferation and the Survival of Mesenchymal and Osteoblast Progenitors

Gadi

Jung

Lee

et al. 2013

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

The Transcription Factor Protein Sox11 Enhances Early Osteoblast Differentiation by Facilitating Proliferation and the Survival of Mesenchymal and Osteoblast Progenitors

Gadi

Jung

Lee

et al. 2013

Journal of Biological Chemistry

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“…(19) Primary mouse calvaria cells were isolated by sequential collagenase digestion and cultured as described. (20) For differentiation studies, C3H10T1/2 mesenchymal stem cells and MC3T3E1 preosteoblasts were seeded in 12-well plates and were fed at confluency with the medium containing the differentiation supplements of 10 mM of bglycerol phosphate (Sigma Chemical Co., St. Louis, MO, USA) and 50 ug/mL of ascorbic acid (Sigma).…”

Section: Cell Culture and Alkaline Phosphatase Stainingmentioning

confidence: 99%

“…Alkaline phosphatase staining (Sigma) was performed as previously described. (19) Transfection of miRNAs…”

Section: Cell Culture and Alkaline Phosphatase Stainingmentioning

confidence: 99%

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miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1

Kim

Park

Jung

et al. 2012

Journal of Bone and Mineral Research

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Uncontrolled oxidative stress impairs bone formation and induces age-related bone loss in humans. The FoxO family is widely accepted to play an important role in protecting diverse cells from reactive oxygen species (ROS). Activation of FoxO1, the main FoxO in bone, stimulates proliferation and differentiation as well as inhibits apoptosis of osteoblast lineage cells. Despite the important role of FoxO1, little is known about how FoxO1 expression in bone is regulated. Meanwhile, several recent studies reported that microRNAs (miRNAs) could play a role in osteoblast differentiation and bone formation by targeting various transcriptional factors. Here, we identified one additional crucial miRNA, miR-182, which regulates osteoblastogenesis by repressing FoxO1 and thereby negatively affecting osteogenesis. Overexpression of miR-182 in osteoblast lineage cells increased cell apoptosis and inhibited osteoblast differentiation, whereas in vivo overexpression of miR-182 in zebrafish impaired bone formation. From in silico analysis and validation experiments, FoxO1 was identified as the target of miR-182, and restoration of FoxO1 expression in miR-182-overexpressing osteoblasts rescued them from the inhibitory effects of miR-182. These results indicate that miR-182 functions as a FoxO1 inhibitor to antagonize osteoblast proliferation and differentiation, with a subsequent negative effect on osteogenesis. To treat bone aging, an antisense approach targeting miR-182 could be of therapeutic value. ß

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Bone‐Targeted Delivery of Cell‐Penetrating‐RUNX2 Fusion Protein in Osteoporosis Model

et al. 2023

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The onset of osteoporosis leads to a gradual decrease in bone density due to an imbalance between bone formation and resorption. To achieve optimal drug efficacy with minimal side effects, targeted drug delivery to the bone is necessary. Previous studies have utilized peptides that bind to hydroxyapatite, a mineral component of bone, for bone‐targeted drug delivery. In this study, a hydroxyapatite binding (HAB) tag is fused to 30Kc19α‐Runt‐related transcription factor 2 (RUNX2) for bone‐targeting. This recombinant protein can penetrate the nucleus of human mesenchymal stem cells (hMSCs) and act as a master transcription factor for osteogenesis. The HAB tag increases the binding affinity of 30Kc19α‐RUNX2 to mineral deposition in mature osteoblasts and bone tissue, without affecting its osteogenic induction capability. In the osteoporosis mouse model, intravenous injection of HAB‐30Kc19α‐RUNX2 results in preferential accumulation in the femur and promotes bone formation while reducing toxicity in the spleen. These findings suggest that HAB‐30Kc19α‐RUNX2 may be a promising candidate for bone‐targeted therapy in osteoporosis.

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The transcription factor snail regulates osteogenic differentiation by repressing Runx2 expression

Cited by 27 publications

References 38 publications

The Transcription Factor Protein Sox11 Enhances Early Osteoblast Differentiation by Facilitating Proliferation and the Survival of Mesenchymal and Osteoblast Progenitors

The Transcription Factor Protein Sox11 Enhances Early Osteoblast Differentiation by Facilitating Proliferation and the Survival of Mesenchymal and Osteoblast Progenitors

miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1

Bone‐Targeted Delivery of Cell‐Penetrating‐RUNX2 Fusion Protein in Osteoporosis Model

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