Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis

Large‐volume bone defects can result from congenital malformation, trauma, infection, inflammation and cancer. At present, it remains challenging to treat these bone defects with clinically available interventions. Allografts, xenografts and most synthetic materials have no intrinsic osteoinductivit...

Full description

Bibliographic Details
Main Authors: Ping Sun, Andi Shi, Chenxi Shen, Yi Liu, Gang Wu, Jianying Feng
Format: Article
Language:English
Published: Wiley 2020-08-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.12906
_version_ 1811295450412613632
author Ping Sun
Andi Shi
Chenxi Shen
Yi Liu
Gang Wu
Jianying Feng
author_facet Ping Sun
Andi Shi
Chenxi Shen
Yi Liu
Gang Wu
Jianying Feng
author_sort Ping Sun
collection DOAJ
description Large‐volume bone defects can result from congenital malformation, trauma, infection, inflammation and cancer. At present, it remains challenging to treat these bone defects with clinically available interventions. Allografts, xenografts and most synthetic materials have no intrinsic osteoinductivity, and so an alternative approach is to functionalize the biomaterial with osteoinductive agents, such as bone morphogenetic protein 2 (BMP2). Because it has been previously demonstrated that human salivary histatin‐1 (Hst1) promotes endothelial cell adhesion, migration and angiogenesis, we examine here whether Hst1 can promote BMP2‐induced bone regeneration. Rats were given subcutaneous implants of absorbable collagen sponge membranes seeded with 0, 50, 200 or 500 μg Hst1 per sample and 0 or 2 μg BMP2 per sample. At 18 days postsurgery, rats were sacrificed, and implanted regional tissue was removed for micro computed tomography (microCT) analyses of new bone (bone volume, trabecular number and trabecular separation). Four samples per group were decalcified and subjected to immunohistochemical staining to analyze osteogenic and angiogenic markers. We observed that Hst1 increased BMP2‐induced new bone formation in a dose‐dependent manner. Co‐administration of 500 μg Hst1 and BMP2 resulted in the highest observed bone volume and trabecular number, the lowest trabecular separation and the highest expression of osteogenic markers and angiogenic markers. Our results suggest that coadministration of Hst1 may enhance BMP2‐induced osteogenesis and angiogenesis, and thus may have potential for development into a treatment for large‐volume bone defects.
first_indexed 2024-04-13T05:32:45Z
format Article
id doaj.art-13cd42a1cf354b3a8a46f5a13fb79c0c
institution Directory Open Access Journal
issn 2211-5463
language English
last_indexed 2024-04-13T05:32:45Z
publishDate 2020-08-01
publisher Wiley
record_format Article
series FEBS Open Bio
spelling doaj.art-13cd42a1cf354b3a8a46f5a13fb79c0c2022-12-22T03:00:22ZengWileyFEBS Open Bio2211-54632020-08-011081503151510.1002/2211-5463.12906Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesisPing Sun0Andi Shi1Chenxi Shen2Yi Liu3Gang Wu4Jianying Feng5The Affiliated Stomatology Hospital Zhejiang University School of Medicine Hangzhou ChinaDepartment of Oral and Maxillofacial Surgery/Pathology Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA) Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS) Amsterdam the NetherlandsLaboratory for Myology Department of Human Movement Sciences Faculty of Behavioural and Movement Sciences Vrije Universiteit Amsterdam (VU), Amsterdam Movement Sciences (AMS) Amsterdam the NetherlandsKey Laboratory of Oral Medicine Guangzhou Institute of Oral Disease Affiliated Stomatology Hospital of Guangzhou Medical University Guangzhou Medical University Guangzhou ChinaDepartment of Oral and Maxillofacial Surgery/Pathology Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA) Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS) Amsterdam the NetherlandsSchool of Dentistry Zhejiang Chinese Medical University Hangzhou ChinaLarge‐volume bone defects can result from congenital malformation, trauma, infection, inflammation and cancer. At present, it remains challenging to treat these bone defects with clinically available interventions. Allografts, xenografts and most synthetic materials have no intrinsic osteoinductivity, and so an alternative approach is to functionalize the biomaterial with osteoinductive agents, such as bone morphogenetic protein 2 (BMP2). Because it has been previously demonstrated that human salivary histatin‐1 (Hst1) promotes endothelial cell adhesion, migration and angiogenesis, we examine here whether Hst1 can promote BMP2‐induced bone regeneration. Rats were given subcutaneous implants of absorbable collagen sponge membranes seeded with 0, 50, 200 or 500 μg Hst1 per sample and 0 or 2 μg BMP2 per sample. At 18 days postsurgery, rats were sacrificed, and implanted regional tissue was removed for micro computed tomography (microCT) analyses of new bone (bone volume, trabecular number and trabecular separation). Four samples per group were decalcified and subjected to immunohistochemical staining to analyze osteogenic and angiogenic markers. We observed that Hst1 increased BMP2‐induced new bone formation in a dose‐dependent manner. Co‐administration of 500 μg Hst1 and BMP2 resulted in the highest observed bone volume and trabecular number, the lowest trabecular separation and the highest expression of osteogenic markers and angiogenic markers. Our results suggest that coadministration of Hst1 may enhance BMP2‐induced osteogenesis and angiogenesis, and thus may have potential for development into a treatment for large‐volume bone defects.https://doi.org/10.1002/2211-5463.12906angiogenesisbone morphogenetic protein 2bone regenerationhistatin‐1osteogenesispeptide
spellingShingle Ping Sun
Andi Shi
Chenxi Shen
Yi Liu
Gang Wu
Jianying Feng
Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis
FEBS Open Bio
angiogenesis
bone morphogenetic protein 2
bone regeneration
histatin‐1
osteogenesis
peptide
title Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis
title_full Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis
title_fullStr Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis
title_full_unstemmed Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis
title_short Human salivary histatin‐1 (Hst1) promotes bone morphogenetic protein 2 (BMP2)‐induced osteogenesis and angiogenesis
title_sort human salivary histatin 1 hst1 promotes bone morphogenetic protein 2 bmp2 induced osteogenesis and angiogenesis
topic angiogenesis
bone morphogenetic protein 2
bone regeneration
histatin‐1
osteogenesis
peptide
url https://doi.org/10.1002/2211-5463.12906
work_keys_str_mv AT pingsun humansalivaryhistatin1hst1promotesbonemorphogeneticprotein2bmp2inducedosteogenesisandangiogenesis
AT andishi humansalivaryhistatin1hst1promotesbonemorphogeneticprotein2bmp2inducedosteogenesisandangiogenesis
AT chenxishen humansalivaryhistatin1hst1promotesbonemorphogeneticprotein2bmp2inducedosteogenesisandangiogenesis
AT yiliu humansalivaryhistatin1hst1promotesbonemorphogeneticprotein2bmp2inducedosteogenesisandangiogenesis
AT gangwu humansalivaryhistatin1hst1promotesbonemorphogeneticprotein2bmp2inducedosteogenesisandangiogenesis
AT jianyingfeng humansalivaryhistatin1hst1promotesbonemorphogeneticprotein2bmp2inducedosteogenesisandangiogenesis