Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells

Baniwal, Sanjeev K.; Shah, Parantu K.; Shi, Yunfan; HaDuong, Josephine H.; DeClerck, Yves A.; Gabet, Yankel; Frenkel, Baruch

doi:10.1007/s00198-011-1728-5

Cited by 43 publications

(61 citation statements)

References 123 publications

(137 reference statements)

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“…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: 82%

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

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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.

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Section: Discussionsupporting

confidence: 82%

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

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“…Sema 7A was the most up-regulated gene among semaphorin family members in hDFCs (Table 1). Previous reports have also confirmed the expression of Sema 7A mRNA in mouse osteoblast cell lines and in primary calvarial osteoblasts 17,26) . We confirmed the gene expression of Sema 7A in hDFCs using RT-PCR and real-time PCR.…”

Section: Expression Of Semaphorin 7a Receptors During Osteogenic Diffsupporting

confidence: 59%

“…Expression of Sema 7A was low at the start of osteoclast culture from spleen-derived cells, and was high during immature osteoclast fusion 17,26) . Sema7A increases cell fusion, as exposure to exogenous Sema 7A during differentiation enhanced the number of nuclei per osteoclast and reduced the number of individual osteoclasts 17) .…”

Section: Expression Of Semaphorin 7a Receptors During Osteogenic Diffmentioning

confidence: 99%

Gene Expression of Semaphorin 7A During Osteogenic Differentiation in Human Dental Follicle Cells

Kato¹,

Takahashi

2016

J. Hard Tissue Biology.

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Semaphorin (Sema) 7A, also known as CDw108, is the only glycophosphatidylinositol (GPI)-linked member of the semaphorin family. It was recently suggested that Sema 7A regulates osteoblast and osteoclast differentiation, and is important for bone homeostasis. The dental follicle is an ectomesenchymal tissue that surrounds developing tooth germ, which contains osteoblastic/cementoblastic lineage committed stem/progenitor cells. The purpose of this study was to examine the gene expression of Sema 7A and its receptors, plexinC1 and -integrin, in human dental follicle cells (hDFCs) during osteogenic differentiation. We analyzed gene expression profiles between hDFCs cultures with GM and OIM on day 17. Sema 7A was the most up-regulated among the semaphorin family members in OIM culture when compared to GM culture. We confirmed the gene expression of Sema 7A in three hDFCs samples isolated from three donors using real-time PCR. Sema 7A was up-regulated in OIM culture in three hDFC samples. In addition, Sema 7A mRNA showed high levels on days 0 and 17 in hDFCs cultured in OIM, as compared to days 3 and 10, exhibiting bimodal expression during osteoblast differentiation. The expression of plexin C1 and -integrin was also up-regulated in OIM culture when compared to GM culture. These findings suggest that Sema 7A and its receptors are associated with the osteogenic differentiation of hDFCs.

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“…Additionally, previous study demonstrated that 12 putative Cbfa1/Runx2-binding elements (osteoblast-specific element 2-OSE 2 ) were presented in human OPG promoter sequence and Runx2 could bind to the proximal OSE 2 to increase OPG expression level [36]. Further, when doxycycline was used to induce increased expression of Runx2 in ST2 cells (a bone marrow-derived mesenchymal pluripotent cell line), the differentiation of cocultured splenocytes into osteoclasts was enhanced along with the inhibition of OPG [37], which result was consistent with our data. Thus, it can be supposed that Runx2 may directly regulate the expression of OPG in PDLSCs.…”

Section: Figmentioning

confidence: 99%

Periodontal Ligament Stem Cells Modulate Root Resorption of Human Primary Teeth via Runx2 Regulating RANKL/OPG System

Wang

Dong

et al. 2014

Stem Cells and Development

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Physiological primary teeth exfoliation is a normal phenomenon during teeth development. However, retained primary teeth can often be observed in the patients with cleidocranial dysplasia (CCD) caused by mutation of Runx2. The potential regulative mechanism is still unknown. In the present study, periodontal ligament stem cells (PDLSCs) were derived from different resorbed stages of primary teeth and permanent teeth from normal patients and primary teeth from CCD patient. The proliferative, osteogenic and osteoclast-inductive capacities of PDLSCs from each group were detected. We demonstrated here that the proliferative ability of PDLSCs was reduced while the osteogenic and the osteoclast-inductive capacity of PDLSCs were enhanced during root resorption. The results also showed that PDLSCs from permanent teeth and CCD patient expressed low level of Runx2 and RANKL while high level of OPG. However, expression of Runx2 and RANKL were increased while expression of OPG was decreased in PDLSCs derived from resorbed teeth. Furthermore, Runx2 regulating the expression of RANKL and OPG and the osteoclast-inductive capacity of PDLSCs were confirmed by gain or loss of function assay. These data suggest that PDLSCs promote osteoclast differentiation via Runx2 upregulating RANKL and downregulating OPG, leading to enhanced root resorption that results in physiological exfoliation of primary teeth.

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Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells

Cited by 43 publications

References 123 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

Gene Expression of Semaphorin 7A During Osteogenic Differentiation in Human Dental Follicle Cells

Periodontal Ligament Stem Cells Modulate Root Resorption of Human Primary Teeth via Runx2 Regulating RANKL/OPG System

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