Cargando…
Identification of osteogenic progenitor cell-targeted peptides that augment bone formation
Activation and migration of endogenous mesenchymal stromal cells (MSCs) are critical for bone regeneration. Here, we report a combinational peptide screening strategy for rapid discovery of ligands that not only bind strongly to osteogenic progenitor cells (OPCs) but also stimulate osteogenic cell A...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453024/ https://www.ncbi.nlm.nih.gov/pubmed/32855388 http://dx.doi.org/10.1038/s41467-020-17417-9 |
_version_ | 1783575276835307520 |
---|---|
author | Jiang, Min Liu, Ruiwu Liu, Lixian Kot, Alexander Liu, Xueping Xiao, Wenwu Jia, Junjing Li, Yuanpei Lam, Kit S. Yao, Wei |
author_facet | Jiang, Min Liu, Ruiwu Liu, Lixian Kot, Alexander Liu, Xueping Xiao, Wenwu Jia, Junjing Li, Yuanpei Lam, Kit S. Yao, Wei |
author_sort | Jiang, Min |
collection | PubMed |
description | Activation and migration of endogenous mesenchymal stromal cells (MSCs) are critical for bone regeneration. Here, we report a combinational peptide screening strategy for rapid discovery of ligands that not only bind strongly to osteogenic progenitor cells (OPCs) but also stimulate osteogenic cell Akt signaling in those OPCs. Two lead compounds are discovered, YLL3 and YLL8, both of which increase osteoprogenitor osteogenic differentiation in vitro. When given to normal or osteopenic mice, the compounds increase mineral apposition rate, bone formation, bone mass, and bone strength, as well as expedite fracture repair through stimulated endogenous osteogenesis. When covalently conjugated to alendronate, YLLs acquire an additional function resulting in a “tri-functional” compound that: (i) binds to OPCs, (ii) targets bone, and (iii) induces “pro-survival” signal. These bone-targeted, osteogenic peptides are well suited for current tissue-specific therapeutic paradigms to augment the endogenous osteogenic cells for bone regeneration and the treatment of bone loss. |
format | Online Article Text |
id | pubmed-7453024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-74530242020-09-04 Identification of osteogenic progenitor cell-targeted peptides that augment bone formation Jiang, Min Liu, Ruiwu Liu, Lixian Kot, Alexander Liu, Xueping Xiao, Wenwu Jia, Junjing Li, Yuanpei Lam, Kit S. Yao, Wei Nat Commun Article Activation and migration of endogenous mesenchymal stromal cells (MSCs) are critical for bone regeneration. Here, we report a combinational peptide screening strategy for rapid discovery of ligands that not only bind strongly to osteogenic progenitor cells (OPCs) but also stimulate osteogenic cell Akt signaling in those OPCs. Two lead compounds are discovered, YLL3 and YLL8, both of which increase osteoprogenitor osteogenic differentiation in vitro. When given to normal or osteopenic mice, the compounds increase mineral apposition rate, bone formation, bone mass, and bone strength, as well as expedite fracture repair through stimulated endogenous osteogenesis. When covalently conjugated to alendronate, YLLs acquire an additional function resulting in a “tri-functional” compound that: (i) binds to OPCs, (ii) targets bone, and (iii) induces “pro-survival” signal. These bone-targeted, osteogenic peptides are well suited for current tissue-specific therapeutic paradigms to augment the endogenous osteogenic cells for bone regeneration and the treatment of bone loss. Nature Publishing Group UK 2020-08-27 /pmc/articles/PMC7453024/ /pubmed/32855388 http://dx.doi.org/10.1038/s41467-020-17417-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Jiang, Min Liu, Ruiwu Liu, Lixian Kot, Alexander Liu, Xueping Xiao, Wenwu Jia, Junjing Li, Yuanpei Lam, Kit S. Yao, Wei Identification of osteogenic progenitor cell-targeted peptides that augment bone formation |
title | Identification of osteogenic progenitor cell-targeted peptides that augment bone formation |
title_full | Identification of osteogenic progenitor cell-targeted peptides that augment bone formation |
title_fullStr | Identification of osteogenic progenitor cell-targeted peptides that augment bone formation |
title_full_unstemmed | Identification of osteogenic progenitor cell-targeted peptides that augment bone formation |
title_short | Identification of osteogenic progenitor cell-targeted peptides that augment bone formation |
title_sort | identification of osteogenic progenitor cell-targeted peptides that augment bone formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453024/ https://www.ncbi.nlm.nih.gov/pubmed/32855388 http://dx.doi.org/10.1038/s41467-020-17417-9 |
work_keys_str_mv | AT jiangmin identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT liuruiwu identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT liulixian identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT kotalexander identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT liuxueping identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT xiaowenwu identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT jiajunjing identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT liyuanpei identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT lamkits identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation AT yaowei identificationofosteogenicprogenitorcelltargetedpeptidesthataugmentboneformation |