Synthetic Osteopontin-derived Peptide SVVYGLR can Induce Neovascularization in Artificial Bone Marrow Scaffold Biomaterials

Hamada, Y.; Egusa, Hiroshi; Kaneda, Yoshitoshi; Hirata, Isao; Kawaguchi, Naomasa; Hirao, Takafumi; Matsumoto, Takuya; Yao, Makiko; Daito, Kiyoshi; Suzuki, M.; Yatani, Hirofumi; Daito, Michiharu; Okazaki, Masanori; Matsuura, Nariaki

doi:10.4012/dmj.26.487

Cited by 48 publications

(40 citation statements)

References 17 publications

(23 reference statements)

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“…A synthetic peptide encompassing the identified motif sequence has been shown to have similar properties in the induction of MCP-1 and MIP-1␤ and in the regulation of the same signaling events in human PBMCs. Interestingly, this motif is apparently different from the known integrinbinding motif, the RGD or SVVYGLR sequences that have been shown to induce other cellular functions, including cell adhesion (34,35). The fact that the GRGDSP sequence motif failed to compete with the identified motif helps rule out the involvement of RGDdependent integrins in this interaction, while the blocking effect of the CD44 antibody further excluded the role of this motif as a receptor for the active sequence motif.…”

Section: Discussionmentioning

confidence: 85%

Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

Zheng¹,

R²,

Pan³

et al. 2009

Arthritis & Rheumatism

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Objective. Osteopontin (OPN) is a proinflammatory protein with a critical role in leukocyte migration. Although OPN has been implicated in rheumatoid arthritis (RA), its underlying mechanism remains unknown. In this study, we investigated the role and molecular mechanism of OPN in the induction of 2 key chemokines, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1␤ (MIP-1␤), in RA.Methods. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction were used to determine chemokine expression. Leukocyte migration in the presence of OPN was measured by chemotaxis assay. Signaling and molecular events were analyzed by immunoblotting and chromatin immunoprecipitation.Results. The effect of OPN on inflammatory cell migration was mediated through its unique property of inducing the expression of MCP-1 and MIP-1␤ in CD14؉ monocytes. The concentration of OPN was significantly elevated in RA patients and appeared to correlate with the serum levels of inflammation markers and increased expression of MCP-1 or MIP-1␤ in monocytes in RA patients. Endogenous production of OPN in RA synovial fluid was attributable to increased production of MCP-1 or MIP-1␤, and this effect could be blocked by an anti-OPN antibody. Furthermore, the structural motif responsible for this property resided within residues 50-83 of human OPN, sparing the known RGD or SVVYGLR sequences. It was evident that the effect of OPN on chemokine expression was mediated through both the NF-B and MAPK pathways, involving the activation of IKK␤, p38, and JNK.Conclusion. These results support a unique role of OPN in leukocyte migration, in the context of perpetuation of rheumatoid synovitis through the induction of MCP-1 and MIP-1␤.

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Section: Discussionmentioning

confidence: 85%

Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

Zheng¹,

R²,

Pan³

et al. 2009

Arthritis & Rheumatism

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“…Interestingly, the SVVYGLR peptide itself has been shown to enhance angiogenesis in both in vivo and in vitro models (Hamada et al , 2003, 2007; Chan et al , 2011). It is unknown whether the SVAYGLK peptide is able to reach the circulation intact; however, our in vitro digestion demonstrates that several short peptides derived from this sequence are generated during digestion.…”

Section: Discussionmentioning

confidence: 99%

Suppression of tumour growth by orally administered osteopontin is accompanied by alterations in tumour blood vessels

Rittling¹,

Wejse

Yagiz³

et al. 2014

Br J Cancer

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Background:The integrin-binding protein osteopontin is strongly associated with tumour development, yet is an abundant dietary component as a constituent of human and bovine milk. Therefore, we tested the effect of orally administered osteopontin (o-OPN) on the development of subcutaneous tumours in mice.Methods:Bovine milk osteopontin was administered in drinking water to tumour-bearing immune-competent mice. Tumour growth, proliferation, necrosis, apoptosis and blood vessel size and number were measured. Expression of the α9 integrin was determined.Results:o-OPN suppressed tumour growth, increased the extent of necrosis, and induced formation of abnormally large blood vessels. Anti-OPN reactivity detected in the plasma of OPN-null mice fed OPN suggested that tumour-blocking peptides were absorbed during digestion, but the o-OPN effect was likely distinct from that of an RGD peptide. Expression of the α9 integrin was detected on both tumour cells and blood vessels. Potential active peptides from the α9 binding site of OPN were identified by mass spectrometry following in vitro digestion, and injection of these peptides suppressed tumour growth.Conclusions:These results suggest that peptides derived from o-OPN are absorbed and interfere with tumour growth and normal vessel development. o-OPN-derived peptides that target the α9 integrin are likely involved.

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“…[137,140] When grafts made of a carbonate-collagen sponge that contained the SWYGLR motif were implanted in a murine bone defect, prominent angiogenesis inside the graft was observed just one week after the implantation. [141] Peptide sequences can also allow cell-type selectivity. This is the particular case of the tetrapeptide Arg-Glu-Asp-Val (REDV), a domain derived from the adhesive protein fibronectin.…”

Section: Microfabrication Of Network With Vascular Geometrymentioning

confidence: 99%

Vascularization in Bone Tissue Engineering: Physiology, Current Strategies, Major Hurdles and Future Challenges

Santos

Reis

2009

Macromolecular Bioscience

381

273

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The lack of a functional vascular supply has, to a large extent, hampered the whole range of clinical applications of 'successful' laboratory-based bone tissue engineering strategies. To the present, grafts have been dependent on post-implant vascularization, which jeopardizes graft integration and often leads to its failure. For this reason, the development of strategies that could effectively induce the establishment of a microcirculation in the engineered constructs has become a major goal for the tissue engineering research community. This review addresses the role and importance of the development of a vascular network in bone tissue engineering and provides an overview of the most up to date research efforts to develop such a network.

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Synthetic Osteopontin-derived Peptide SVVYGLR can Induce Neovascularization in Artificial Bone Marrow Scaffold Biomaterials

Cited by 48 publications

References 17 publications

Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF‐κB and MAPK pathways in rheumatoid arthritis

Suppression of tumour growth by orally administered osteopontin is accompanied by alterations in tumour blood vessels

Vascularization in Bone Tissue Engineering: Physiology, Current Strategies, Major Hurdles and Future Challenges

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