Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway

Zhang, Lianfang; Qi, Jin; Zuo, Guilai; Jia, Peng; Shen, Xing; Shao, Jian Yong; Kang, Hui; Yang, Huilin; Deng, Lianfu

doi:10.1371/journal.pone.0099946

Cited by 28 publications

(27 citation statements)

References 38 publications

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“…To investigate whether the observed defect in mineralization in male OBVEGFKO mice was driven by direct effects of VEGF on LOB function, we deleted VEGF with adenovirus-Cre-GFP as previously described. (26) Consistent with our previous work, (29) LOBs did not express detectable levels of VEGFR2 protein or mRNA (Supplemental Fig. S8A, C).…”

Section: In Vitro Vegf Deletion Induces Distinct Matrix and Mineralizsupporting

confidence: 91%

“…In vitro deletion of osteoblast-derived VEGF Once 80% confluent, LOBs were treated with adenovirus-Cre-GFP (Vector Laboratories, Burlingame, CA, USA) in growth media containing 10% FBS for deletion of VEGF or adenovirus-GFP as a control at a multiplicity of infection of 100 for 6 days. (26) For cell viability/proliferation only, LOBs were treated with Adenovirus-Cre-GFP (denoted OBVEGFKO) and Adenovirus-GFP (denoted WT) for 24 hours. For collection of conditioned media (CM), cells were stepped down in lowserum media (1%) for 24 hours.…”

Section: Scanning Electron Microscopy (Sem)mentioning

confidence: 99%

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Regulation of the Bone Vascular Network is Sexually Dimorphic

Goring

Sharma

Javaheri

et al. 2019

Journal of Bone and Mineral Research

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Osteoblast (OB) lineage cells are an important source of vascular endothelial growth factor (VEGF), which is critical for bone growth and repair. During bone development, pubertal differences in males and females exist, but little is known about whether VEGF signaling contributes to skeletal sexual dimorphism. We have found that in mice, conditional disruption of VEGF in osteocalcin‐expressing cells (OcnVEGFKO) exerts a divergent influence on morphological, cellular, and whole bone properties between sexes. Furthermore, we describe an underlying sexual divergence in VEGF signaling in OB cultures in vitro independent of circulating sex hormones. High‐resolution synchrotron computed tomography and backscattered scanning electron microscopy revealed, in males, extensive unmineralized osteoid encasing enlarged blood vessel canals and osteocyte lacunae in cortical bone after VEGF deletion, which contributed to increased porosity. VEGF was deleted in male and female long bone–derived OBs (OBVEGKO) in vitro and Raman spectroscopic analyses of mineral and matrix repertoires highlighted differences between male and female OBVEGFKO cells, with increased immature phosphate species prevalent in male OBVEGFKO cultures versus wild type (WT). Further sexual dimorphism was observed in bone marrow endothelial cell gene expression in vitro after VEGF deletion and in sclerostin protein expression, which was increased in male OcnVEGFKO bones versus WT. The impact of altered OB matrix composition after VEGF deletion on whole bone geometry was assessed between sexes, although significant differences between OcnVEGFKO and WT were identified only in females. Our results suggest that bone‐derived VEGF regulates matrix mineralization and vascularization distinctly in males and females, which results in divergent physical bone traits.

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Section: In Vitro Vegf Deletion Induces Distinct Matrix and Mineralizsupporting

confidence: 91%

Section: Scanning Electron Microscopy (Sem)mentioning

confidence: 99%

Regulation of the Bone Vascular Network is Sexually Dimorphic

Goring

Sharma

Javaheri

et al. 2019

Journal of Bone and Mineral Research

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“…It was noted that there was no new bone formation in this study. Similarly, Zhang et al 42 found that the single VEGF from the silk gel or silk scaffold only promoted angiogenesis and more tissue infiltration into the gel or scaffold, in which no bone regeneration was observed, while combining VEGF and BMP-2 released from the silk gel or silk scaffold could promote angiogenesis and new bone formation. 48,49 Besides, graft motion in the bone tunnel could be inevitable in ACL reconstruction model, which impeded bone regeneration.…”

mentioning

confidence: 95%

“…41 The proliferation level of BMSCs in the UHMWPE-SF/VEGF group was significantly higher than that of the UHMWPE-SF group after 14-day cultivation, because the sustained VEGF release was conductive to BMSC proliferation and adhesion. Zhang et al 42 demonstrated that VEGF stimulated the proliferation and osteogenic differentiation of BMSC by promoting the expression of heme oxygenase-1. Besides, VEGF regulated BMSC fate by increasing osteoblast differentiation and reducing adipocyte differentiation.…”

mentioning

confidence: 99%

Surface modification of vascular endothelial growth factor-loaded silk fibroin to improve biological performance of ultra-high-molecular-weight polyethylene via promoting angiogenesis

Ai¹,

Sheng²,

Cai³

et al. 2017

IJN

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Ultra-high-molecular-weight polyethylene (UHMWPE) has been applied in orthopedics, as the materials of joint prosthesis, artificial ligaments, and sutures due to its advantages such as high tensile strength, good wear resistance, and chemical stability. However, postoperative osteolysis induced by UHMWPE wear particles and poor bone–implant healing interface due to scarcity of osseointegration is a significant problem and should be solved imperatively. In order to enhance its affinity to bone tissue, vascular endothelial growth factor (VEGF) was loaded on the surface of materials, the loading was performed by silk fibroin (SF) coating to achieve a controlled-release delivery. Several techniques including field emission scanning electron microscopy (FESEM) and attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) and water contact angle measurement were used to validate the effectiveness of introduction of SF/VEGF. The result of ELISA demonstrated that the release of VEGF was well maintained up to 4 weeks. The modified UHMWPE was evaluated by both in vitro and in vivo experiments. According to the results of FESEM and cell counting kit-8 (CCK-8) assay, bone marrow mesenchymal stem cells cultured on the UHMWPE coated with SF/VEGF and SF exhibited a better proliferation performance than that of the pristine UHMWPE. The model rabbit of anterior cruciate ligament reconstruction was used to observe the graft–bone healing process in vivo. The results of histological evaluation, microcomputed tomography (micro-CT) analysis, and biomechanical tests performed at 6 and 12 weeks after surgery demonstrated that graft–bone healing could be significantly improved due to the effect of VEGF on angiogenesis, which was loaded on the surface by SF coating. This study showed that the method loading VEGF on UHMWPE by SF coating played an effective role on the biological performance of UHMWPE and displayed a great potential application for anterior cruciate ligament reconstruction.

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“…On the contrary, HO-1 expression induced by Hemin accelerated the cell cycle progression to G2/M phase (Fig. 3), probably by promoting cell proliferation and differentiation (15,16). ylation (17,18).…”

Section: Aza Treatment Increases Ho-1 Expression In Skm-1 Cellsmentioning

confidence: 96%

Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation

Wang

et al. 2015

International Journal of Oncology

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Heme oxygenase-1 was reported previously as a resistance target on acute myelocytic leukemia (AML). We found that HO-1 was resistant to 5-azacytidine (AZA) treatment of myelodysplastic syndrome (MDS), and explored further the relative mechanisms. Patient bone marrow mononuclear cells (n=48) diagnosed as different levels of MDS were collected. Cell growth was evaluated by MTT assay; cell cycle and apoptosis were detected by flow cytometry; mRNA expression was assessed by real-time PCR, protein expression was analyzed through western blotting. Methylation was assessed by MSP. The survival time, and weight of mice were recorded. HO-1 overexpression was observed in SKM-1 cells after AZA treatment comparing to other cell lines. The HO-1 expression in MDS patients with high-risk was higher than in low-risk patients. After HO-1 was silenced by lentivirus-mediated siRNA, the proliferation of SKM-1 cells was effectively inhibited by low concentration AZA, and the cell cycle was arrested in the G0/G1 phase. Upregulation of p16 and changing of p16-relative cell cycle protein was observed after silencing HO-1 in AZA treated SKM-1 cells. In addition, DNMT1 was downregulated following the decrease of HO-1 expression. In vivo, silencing HO-1 inhibited SKM-1 cell growth induced by AZA in a NOD/SCID mouse model. Silencing HO-1 sensitized SKM-1 cells toward AZA, which may be attributed to the influence of HO-1 on AZA-induced p16 demethylation. HO-1 may be one of the targets that enhance the therapeutic effects of AZA on MDS malignant transformation inspiring new treatment methods for high-risk and very high-risk MDS patients in clinical practice.

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Osteoblast-Secreted Factors Promote Proliferation and Osteogenic Differentiation of Bone Marrow Stromal Cells via VEGF/Heme-Oxygenase-1 Pathway

Cited by 28 publications

References 38 publications

Regulation of the Bone Vascular Network is Sexually Dimorphic

Regulation of the Bone Vascular Network is Sexually Dimorphic

Surface modification of vascular endothelial growth factor-loaded silk fibroin to improve biological performance of ultra-high-molecular-weight polyethylene via promoting angiogenesis

Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation

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