Glucocorticoids Antagonize RUNX2 During Osteoblast Differentiation in Cultures of ST2 Pluripotent Mesenchymal Cells

Koromila, Theodora; Baniwal, Sanjeev K.; Song, Yae S.; Martín, Anthony R.; Xiong, Jian; Frenkel, Baruch

doi:10.1002/jcb.24646

Cited by 48 publications

(55 citation statements)

References 28 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, we discovered that the expression of Runx2 was decreased post-MP treatment, whereas it was upregulated after the transplantation of SDF-1α-GFP-BMSCs, which is consistent with the results of previous studies [52, 53]. Lingqian et al reported that the cotherapy with the parathyroid hormone (PTH) and SDF-1 promoted osteogenic differentiation of human periodontal ligament stem cells by enhancing OCN expression and ALP activity [54], which is in line with the findings of the present study.…”

Section: Discussionsupporting

confidence: 93%

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

Yang

Xue

Guan

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Osteonecrosis of the femoral head (ONFH) is a devastating orthopedic disease. Previous studies suggested that stromal-cell-derived factor (SDF)-1 was involved in osteogenesis and angiogenesis. However, whether SDF-1 potentiates the angiogenesis and osteogenesis of bone marrow-derived stromal stem cells (BMSCs) in ONFH is not clear. Methods: BMSCs were transfected with green fluorescent protein (GFP) or the fusion gene encoding GFP and SDF-1α, and transgenic efficacy was monitored by immunofluorescence. The expression of SDF-1α, runt-related transcription factor 2 (Runx2, osteocalcin (OCN), and alkaline phosphatase (ALP) at the mRNA level was measured by real-time polymerase chain reactions (RT-PCR). The expression of SDF-1α, Runx2, OCN, and p-Smad1/5 were measured at the protein level by Western blot. Transwell migration assay and tube formation assay were utilized to detect the angiogenesis in vitro, whereas the in vivo angiogenesis was monitored by angiography. Immunohistological staining and micro-CT scanning were conducted to assess the histological changes in morphology. Results: In vitro, SDF-1α overexpression in BMSCs promoted osteogenic differentiation and upregulated the expression of osteogenic-related proteins, such as ALP, Runx2, OCN, and p-Smadl/5. In the methylprednisolone induced ONFH rat model used in our investigation, the overexpression of SDF-1α in BMSCs promoted significantly more bone regeneration and the expression of OCN and Runx2 as compared with the effect of vehicle overexpression. Moreover, the morphology of ONFH was ameliorated after the transplantation of BMSCs with SDF-1α overexpression. Furthermore, SDF-1α overexpression in BMSCs significantly increased osteoblastic angiogenesis as indicated by the increased tube formation ability, CD31 expression, and vessel volume. Conclusion: SDF-1α overexpression in BMSCs promotes bone generation as indicated by osteogenesis and angiogenesis, suggesting SDF-1α may serve as a therapeutic drug target for ONFH treatment.

show abstract

Section: Discussionsupporting

confidence: 93%

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

Yang

Xue

Guan

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…However, we hypothesized that the presence of Tubacin have altered protein-protein interaction or possibly recruited another molecule for competitive binding relieving this repressive effect of GR on OCN thus driving OCN gene expression. We speculated that this molecule is RUNX2 since it has been reported to interact with HDAC655, a physical interaction exists between RUNX2 and the GC receptor (GR)56 and the proximal and distal regions of the OCN promoter has a Runx2 and TCF/LEF binding sites, and is responsible for basal tissue specific41 and enhanced transcriptional transcription33 respectively. Furthermore, RUNX2 is known to either act as an activator or repressor depending on the regulatory proteins bound to it57.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid receptor and Histone deacetylase 6 mediate the differential effect of dexamethasone during osteogenesis of mesenchymal stromal cells (MSCs)

Rimando

Wu²,

Liu

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Lineage commitment and differentiation of mesenchymal stromal cells (MSCs) into osteoblasts in vitro is enhanced by a potent synthetic form of glucocorticoid (GC), dexamethasone (Dex). Paradoxically, when used chronically in patients, GCs exert negative effects on bone, a phenomenon known as glucocorticoid-induced osteoporosis in clinical practice. The mechanism on how GC differentially affects bone precursor cells to become mature osteoblasts during osteogenesis remains elusive. In this study, the dose and temporal regulation of Dex on MSC differentiation into osteoblasts were investigated. We found that continuous Dex treatment led to a net reduction of the maturation potential of differentiating osteoblasts. This phenomenon correlated with a decrease in glucocorticoid receptor (GR) expression, hastened degradation, and impaired sub cellular localization. Similarly, Histone Deacetylase 6 (HDAC6) expression was found to be regulated by Dex, co-localized with GR and this GR-HDAC6 complex occupied the promoter region of the osteoblast late marker osteocalcin (OCN). Combinatorial inhibition of HDAC6 and GR enhanced OCN expression. Together, the cross-talk between the Dex effector molecule GR and the inhibitory molecule HDAC6 provided mechanistic explanation of the bimodal effect of Dex during osteogenic differentiation of MSCs. These findings may provide new directions of research to combat glucocorticoid-induced osteoporosis.

show abstract

“…These complications are partially attributed to modifications in the bioactivity of bone marrow-derived stem cells, osteoblasts/osteocytes and osteoclasts (2–4). Previous studies have indicated that GCs antagonize Runt-related transcription factor 2 (Runx2) during the osteoblast differentiation of mesenchymal cells and inhibit the osteogenesis of bone marrow-derived stem cells (3,5). GCs have also been reported to directly suppress the osteogenic differentiation of osteoblasts (6), induce osteoblast and osteocyte apoptosis, and decrease the number of bone-forming cells (7–9).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of VK2 on glucocorticoid-treated MC3T3-E1 cells

Zhang¹,

Yin²,

Ding³

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Glucocorticoids (GCs) contribute to the increased incidence of secondary osteoporosis and osteonecrosis, and medications for the prevention and treatment of these complications have been investigated for many years. Vitamin K2 (VK2) has been proven to promote bone formation both in vitro and in vivo. In this study, we examined the effects of VK2 on dexamethasone (DEX)-treated MC3T3-E1 osteoblastic cells. We observed that VK2 promoted the proliferation and enhanced the survival of dexamethasone-treated MC3T3-E1 cells. In addition, VK2 upregulated the expression levels of osteogenic marker proteins, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin, which were significantly inhibited by dexamethasone. On the whole, our findings indicate that VK2 has the potential to antagonize the effects of GCs on MC3T3-E1 cells, and may thus prove to be a promising agent for the prevention and treatment of GC-induced osteoporosis and osteonecrosis.

show abstract

Glucocorticoids Antagonize RUNX2 During Osteoblast Differentiation in Cultures of ST2 Pluripotent Mesenchymal Cells

Cited by 48 publications

References 28 publications

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head

Glucocorticoid receptor and Histone deacetylase 6 mediate the differential effect of dexamethasone during osteogenesis of mesenchymal stromal cells (MSCs)

Protective effect of VK2 on glucocorticoid-treated MC3T3-E1 cells

Contact Info

Product

Resources

About