Angiogenesis-osteogenesis coupling: a key element in bone physiology and regeneration

Boston, Bridget; Ipe, Deepak S.; Capitanescu, Bogdan; Hamlet, Stephen; Love, Robert M.; Nusem, Iulian; Miroiu, Rodica; Warnke, Patrick H.; Petcu, Eugen Bogdan

doi:10.24238/13221-13-1-203

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…Large numbers of studies have highlighted the vital roles of coupled angiogenesis and osteogenesis during bone healing process, particular for the cross-talk between endothelial cells and osteogenic cells [ 30 , 31 ]. Recently, papers also demonstrated that, apart from proosteogenesis, CGRP also displayed a potential promotive role in angiogenesis and vasodilatory of injury bone site, which in turn indirectly promote osteogenesis [ 13 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Neural Peptide α-CGRP Coregulated Angiogenesis and Osteogenesis via Promoting the Cross-Talk between Mesenchymal Stem Cells and Endothelial Cells

Shi

Wang

Deng

et al. 2022

BioMed Research International

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Background. The coupled vascularization and bone remodeling are key steps during bone healing, during which the cross-talk between mesenchymal stem cells (MSCs) and endothelial cells plays vital roles. Evidence indicates the well-characterized neuropeptide Calcitonin Gene-Related Peptide-α (CGRP) is proven to play an important role during bone regeneration. However, the regulatory effects of αCGRP on angiogenesis and osteogenesis, as well as underlying cellular and molecular mechanisms, remain unclear. Aim. The present study was performed to verify the availability of the CGRP for osteogenic capacity in MSCs and explore its potential underlying molecular mechanism. After that, the promoted angiogenic effect of CGRP as well as its underlying mechanisms was studied. Methods and Results. The results showed that CGRP could significantly increase the cyclic adenosine monophosphate (cAMP) level and promote the osteogenesis ability of MSCs via cAMP/PKA signaling pathway. Direct exposure to CGRP increased nitric oxide synthase expression, the release of NO, tube formation, and wound healing of human umbilical vein endothelial cells (HUVEC). The CGRP-treated MSCs were observed with high expression levels of angiogenic factors, such as bFGF and VEGF-α; the conditioned medium derived from CGRP-treated MSCs was also able to promote tube formation and transmembrane migration of HUVECs. Conclusion. These findings demonstrate the coregulated angiogenesis and osteogenesis effects of CGRP, especially for its regulation effects on the cross-talk between mesenchymal stem cells and endothelial cells.

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Section: Discussionmentioning

confidence: 99%

Neural Peptide α-CGRP Coregulated Angiogenesis and Osteogenesis via Promoting the Cross-Talk between Mesenchymal Stem Cells and Endothelial Cells

Shi

Wang

Deng

et al. 2022

BioMed Research International

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“…( DiPietro, 2016 ; Shi et al, 2023 ). During bone development and regeneration, the growth of blood vessels are coupled with osteogenesis ( Boston et al, 2021 ; Schott et al, 2021 ). Blood vessels are important for the transport of nutrients, oxygen, ions, circulating cells and facilitate the removal of metabolic waste ( Rademakers et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Dentin matrix protein 1 and HUVEC-ECM scaffold promote the differentiation of human dental pulp stem cells into endothelial lineage: implications in regenerative medicine

Ganapathy,

Narayanan,

Chen

et al. 2024

Front. Physiol.

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Reprograming of the dental pulp somatic cells to endothelial cells is an attractive strategy for generation of new blood vessels. For tissue regeneration, vascularization of engineered constructs is crucial to improve repair mechanisms. In this study, we show that dentin matrix protein 1 (DMP1) and HUVEC-ECM scaffold enhances the differentiation potential of dental pulp stem cells (DPSCs) to an endothelial phenotype. Our results show that the differentiated DPSCs expressed endothelial markers CD31 and VE-Cadherin (CD144) at 7 and 14 days. Expression of CD31 and VE-Cadherin (CD144) were also confirmed by immunofluorescence. Furthermore, flow cytometry analysis revealed a steady increase in CD31 and VE-Cadherin (CD144) positive cells with DMP1 treatment when compared with control. In addition, integrins specific for endothelial cells were highly expressed during the differentiation process. The endothelial cell signature of differentiated DPSCs were additionally characterized for key endothelial cell markers using gene expression by RT-PCR, Western blotting, immunostaining, and RNA-seq analysis. Furthermore, the angiogenic phenotype was confirmed by tubule and capillary sprout formation. Overall, stimulation of DPSCs by DMP1 and use of HUVEC-ECM scaffold promoted their differentiation into phenotypically, transcriptionally, and functionally differentiated bonafide endothelial cells. This study is novel, physiologically relevant and different from conventional strategies.

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Injectable hydrogel scaffold incorporating microspheres containing cobalt‐doped bioactive glass for bone healing

Ghiasi Tabari,

Sattari,

Mashhadi Keshtiban

et al. 2024

J Biomedical Materials Res

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Injectable in situ‐forming scaffolds that induce both angiogenesis and osteogenesis have been proven to be promising for bone healing applications. Here, we report the synthesis of an injectable hydrogel containing cobalt‐doped bioactive glass (BG)‐loaded microspheres. Silk fibroin (SF)/gelatin microspheres containing BG particles were fabricated through microfluidics. The microspheres were mixed in an injectable alginate solution, which formed an in situ hydrogel by adding CaCl2. The hydrogel was evaluated for its physicochemical properties, in vitro interactions with osteoblast‐like and endothelial cells, and bone healing potential in a rat model of calvarial defect. The microspheres were well‐dispersed in the hydrogel and formed pores of >100 μm. The hydrogel displayed shear‐thinning behavior and modulated the cobalt release so that the optimal cobalt concentration for angiogenic stimulation, cell proliferation, and deposition of mineralized matrix was only achieved by the scaffold that contained BG doped with 5% wt/wt cobalt (A‐S‐G5Co). In the scaffold containing higher cobalt content, a reduced biomimetic mineralization on the surface was observed. The gene expression study indicated an upregulation of the osteogenic genes of COL1A1, ALPL, OCN, and RUNX2 and angiogenic genes of HIF1A and VEGF at different time points in the cells cultured with the A‐S‐G5Co. Finally, the in vivo study demonstrated that A‐S‐G5Co significantly promoted both angiogenesis and osteogenesis and improved bone healing after 12 weeks of follow‐up. These results show that incorporation of SF/gelatin microspheres containing cobalt‐doped BG in an injectable in situ‐forming scaffold can effectively enhance its bone healing potential through promotion of angiogenesis and osteogenesis.

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Angiogenesis-osteogenesis coupling: a key element in bone physiology and regeneration

Cited by 3 publications

References 35 publications

Neural Peptide α-CGRP Coregulated Angiogenesis and Osteogenesis via Promoting the Cross-Talk between Mesenchymal Stem Cells and Endothelial Cells

Neural Peptide α-CGRP Coregulated Angiogenesis and Osteogenesis via Promoting the Cross-Talk between Mesenchymal Stem Cells and Endothelial Cells

Dentin matrix protein 1 and HUVEC-ECM scaffold promote the differentiation of human dental pulp stem cells into endothelial lineage: implications in regenerative medicine

Injectable hydrogel scaffold incorporating microspheres containing cobalt‐doped bioactive glass for bone healing

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