Role and regulation of RUNX2 in osteogenesis

Bruderer, Marco; Richards, Rebecca; Alini, Mauro; Stoddart, M J

doi:10.22203/ecm.v028a19

Cited by 490 publications

(403 citation statements)

References 162 publications

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“…Runx2 plays an essential role in the differentiation of immature osteoblast and is regarded as an early marker of osteoblast. 24 In this study, we found that …”

Section: Protein Expressionmentioning

confidence: 59%

Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects

Zhou

Chen

et al. 2017

IJN

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Hydroxyapatite (HAP; Ca 10 (PO 4 ) 6 (OH) 2 ) and whitlockite (WH; Ca 18 Mg 2 (HPO 4 ) 2 (PO 4 ) 12 ) are widely utilized in bone repair because they are the main components of hard tissues such as bones and teeth. In this paper, we synthesized HAP and WH hollow microspheres by using creatine phosphate disodium salt as an organic phosphorus source in aqueous solution through microwave-assisted hydrothermal method. Then, we prepared HAP/chitosan and WH/chitosan composite membranes to evaluate their biocompatibility in vitro and prepared porous HAP/chitosan and WH/chitosan scaffolds by freeze drying to compare their effects on bone regeneration in calvarial defects in a rat model. The experimental results indicated that the WH/chitosan composite membrane had a better biocompatibility, enhancing proliferation and osteogenic differentiation ability of human mesenchymal stem cells than HAP/chitosan. Moreover, the porous WH/chitosan scaffold can significantly promote bone regeneration in calvarial defects, and thus it is more promising for applications in tissue engineering such as calvarial repair compared to porous HAP/chitosan scaffold.

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“…Runx2 plays an essential role in the differentiation of immature osteoblast and is regarded as an early marker of osteoblast. 24 In this study, we found that …”

Section: Protein Expressionmentioning

confidence: 59%

Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects

Zhou

Chen

et al. 2017

IJN

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“…As can be seen in Figure 7, after a single day of LCN2 exposure, the expression of runt-related transcription factor 2 (RUNX2), a master transcription factor associated with osteoblast differentiation, [20][21][22][23] was significantly increased ( Figure 7A). Similarly, the expression of TGF-b and VEGF transcripts (growth factors known to be important in remodeling the MF microenvironment) [24][25][26] was also increased ( Figure 7B), whereas bone morphogenetic protein 2 (BMP2), a member of the TGF-b superfamily involved in osteoblast differentiation, [25][26][27] was increased on day 1 and day 6 of culture.…”

Section: The Effects Of Lcn2 On Msc Gene Expressionmentioning

confidence: 95%

“…Similarly, the expression of TGF-b and VEGF transcripts (growth factors known to be important in remodeling the MF microenvironment) [24][25][26] was also increased ( Figure 7B), whereas bone morphogenetic protein 2 (BMP2), a member of the TGF-b superfamily involved in osteoblast differentiation, [25][26][27] was increased on day 1 and day 6 of culture. In addition, 2 known products of osteoblasts, osteoprotegerin (OPG) and collagen type 1(COL1A1), 20,21 were also increased after incubation with LCN2 ( Figure 7C). By contrast, incubation with LCN2 markedly decreased PPARg gene expression, which is associated with adipogenesis ( Figure 7D).…”

Section: The Effects Of Lcn2 On Msc Gene Expressionmentioning

confidence: 95%

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Lü

Xia

Liu

et al. 2015

Blood

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Key Points• LCN2 acts to generate reactive oxygen species, leading to increased DNA strand breaks and apoptosis in normal CD34 1 cells.• LCN2 promotes the generation of osteoblasts but diminishes adipogenesis, resembling the composition of the MF marrow microenvironment.Myelofibrosis (MF) is characterized by cytopenias, constitutional symptoms, splenomegaly, and marrow histopathological abnormalities (fibrosis, increased microvessel density, and osteosclerosis). The microenvironmental abnormalities are likely a consequence of the elaboration of a variety of inflammatory cytokines generated by malignant megakaryocytes and monocytes. We observed that levels of a specific inflammatory cytokine, lipocalin-2 (LCN2), were elevated in the plasmas of patients with myeloproliferative neoplasms (MF > polycythemia vera or essential thrombocythemia) and that LCN2 was elaborated by MF myeloid cells. LCN2 generates increased reactive oxygen species, leading to increased DNA strand breaks and apoptosis of normal, but not MF, CD34 1 cells. Furthermore, incubation of marrow adherent cells or mesenchymal stem cells with LCN2 increased the generation of osteoblasts and fibroblasts, but not adipocytes. LCN2 priming of mesenchymal stem cells resulted in the upregulation of RUNX2 gene as well as other genes that are capable of further affecting osteoblastogenesis, angiogenesis, and the deposition of matrix proteins. These data indicate that LCN2 is an additional MF inflammatory cytokine that likely contributes to the creation of a cascade of events that results in not only a predominance of the MF clone but also a dysfunctional microenvironment. (Blood. 2015;126(8):972-982)

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“…RUNX2 sumoylation, ubiquitination, and acetylation are tightly linked with protein stability (3,14), and acetylated RUNX2 shows increased transactivation activity (14). Phosphorylation is a common protein modification.…”

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confidence: 99%

Cystathionine γ-Lyase–Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby Increasing Osteoblast Activity to Promote Bone Fracture Healing

Zheng

Liao

Lin

et al. 2017

Antioxidants & Redox Signaling

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Aims: Hydrogen sulfide (H2S) plays an essential role in bone formation, in part, by inhibiting osteoclast differentiation, maintaining mesenchymal stem cell osteogenesis ability, or reducing osteoblast injury. We aimed to investigate the role of H2S in osteoblast function and its possible molecular target. Results: In this study, we found that cystathionine c-lyase (CSE) majorly contributed to endogenous H2S production in the primary osteoblast. Overexpressed CSE increased osteoblast differentiation and maturation with higher bone morphogenetic protein 2 and osteopontin expression, alkaline phosphatase activity, and calcium nodule formation; in contrast, knockdown of CSE had opposite effects. Runt-related transcript factor 2 (RUNX2) is required for osteoblast biologic function. CSE-H2S increased nuclear RUNX2 accumulation, DNA binding activity, and target gene transcription. Protein sulfhydration is a common signal by H2S. We confirmed that RUNX2 was also sulfhydrated by H2S. This chemical modification enhanced RUNX2 transactivation, which was blocked by dithiothreitol (DTT, sulfhydration remover). Mutation of two cysteine sites in the runt domain of RUNX2 abolished H2S-induced RUNX2 sulfhydration and transactivation. In a bone -fracture rat model, overexpressed CSE promoted bone healing, which confirmed the effect of CSE-H2S on osteoblasts. Innovation: CSE-H2S is a dominant H2S generation system in osteoblasts and promotes osteoblast activity by the RUNX2 pathway, with RUNX2 sulfhydration as a novel transactivation regulation. Conclusion: CSE-H2S sulfhydrated RUNX2 enhanced its transactivation and increased osteoblast differentiation and maturation, thereby promoting bone healing. Antioxid. Redox Signal. 27, 742-753.

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Role and regulation of RUNX2 in osteogenesis

Cited by 490 publications

References 162 publications

Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects

Comparative study of porous hydroxyapatite/chitosan and whitlockite/chitosan scaffolds for bone regeneration in calvarial defects

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

Cystathionine γ-Lyase–Hydrogen Sulfide Induces Runt-Related Transcription Factor 2 Sulfhydration, Thereby Increasing Osteoblast Activity to Promote Bone Fracture Healing

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