The effect of experimental diabetes and glycaemic control on guided bone regeneration:   histology and gene expression analyses

M Retzepi; E Calciolari; I Wall; M P Lewis; N Donos

doi:10.1111/clr.13031

The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses

M Retzepi
, E Calciolari
, I Wall
, M P Lewis
, N Donos

Centre for Oral Clinical Research, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, UK.
National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK.

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

65 Downloads (Pure)

Abstract

OBJECTIVES: To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR).

MATERIAL AND METHODS: Ninety-three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5-mm defect was created at the mid-portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis.

RESULTS: Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38-42%) and newly formed bone (54-61%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified.

CONCLUSIONS: Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population.

Original language	English
Pages (from-to)	139-154
Number of pages	16
Journal	Clinical oral implants research
Volume	29
Issue number	2
Early online date	18 Jul 2017
DOIs	https://doi.org/10.1111/clr.13031
Publication status	Published - 1 Feb 2018

Bibliographical note

This is the peer reviewed version of the following article: Retzepi, M, Calciolari, E, Wall, I, Lewis, MP, Donos, N. The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses. Clin. Oral Impl. Res. 29, 2018, 139– 154, which has been published in final form at https://doi.org/10.1111/clr.13031. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Animals
Bone Regeneration
Diabetes Mellitus, Experimental/complications
Gene Expression Profiling
Guided Tissue Regeneration
Male
Parietal Bone/growth & development
Rats
Rats, Wistar

Access to Document

10.1111/clr.13031

The effect of experimental diabetes and glycaemic control on guided bone regeneration
This is the peer reviewed version of the following article: Retzepi, M, Calciolari, E, Wall, I, Lewis, MP, Donos, N. The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses. Clin. Oral Impl. Res. 29, 2018, 139– 154, which has been published in final form at https://doi.org/10.1111/clr.13031. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Accepted author manuscript, 1.25 MB

Cite this

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title = "The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses",

abstract = "OBJECTIVES: To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR).MATERIAL AND METHODS: Ninety-three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5-mm defect was created at the mid-portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis.RESULTS: Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38-42\%) and newly formed bone (54-61\%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified.CONCLUSIONS: Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population.",

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author = "M Retzepi and E Calciolari and I Wall and Lewis, \{M P\} and N Donos",

note = "This is the peer reviewed version of the following article: Retzepi, M, Calciolari, E, Wall, I, Lewis, MP, Donos, N. The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses. Clin. Oral Impl. Res. 29, 2018, 139– 154, which has been published in final form at https://doi.org/10.1111/clr.13031. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.",

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T1 - The effect of experimental diabetes and glycaemic control on guided bone regeneration

T2 - histology and gene expression analyses

AU - Retzepi, M

AU - Calciolari, E

AU - Wall, I

AU - Lewis, M P

AU - Donos, N

N1 - This is the peer reviewed version of the following article: Retzepi, M, Calciolari, E, Wall, I, Lewis, MP, Donos, N. The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses. Clin. Oral Impl. Res. 29, 2018, 139– 154, which has been published in final form at https://doi.org/10.1111/clr.13031. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.

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N2 - OBJECTIVES: To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR).MATERIAL AND METHODS: Ninety-three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5-mm defect was created at the mid-portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis.RESULTS: Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38-42%) and newly formed bone (54-61%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified.CONCLUSIONS: Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population.

AB - OBJECTIVES: To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR).MATERIAL AND METHODS: Ninety-three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5-mm defect was created at the mid-portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis.RESULTS: Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38-42%) and newly formed bone (54-61%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified.CONCLUSIONS: Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population.

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KW - Bone Regeneration

KW - Diabetes Mellitus, Experimental/complications

KW - Gene Expression Profiling

KW - Guided Tissue Regeneration

KW - Male

KW - Parietal Bone/growth & development

KW - Rats

KW - Rats, Wistar

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JO - Clinical oral implants research

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