The impact of low-dose irradiation on attenuation of inflammation and bone metabolism: osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Erlangen ; Nürnberg
[2017]
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | 145 Seiten Illustrationen, Diagramme |
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| 245 | 1 | 0 | |a The impact of low-dose irradiation on attenuation of inflammation and bone metabolism |b osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem |c vorgelegt von Lisa Janina Deloch aus Nürnberg |
| 246 | 1 | 1 | |a Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel |
| 264 | 1 | |a Erlangen ; Nürnberg |c [2017] | |
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| 502 | |b Dissertation |c Friedrich-Alexander-Universität Erlangen-Nürnberg |d 2017 | ||
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Record in the Search Index
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| adam_text | TABLE OF CONTENTS
1. SUM M
ARY............................................................................................................................................
8
1.1 SUM
MARY............................................................................................................................................
8
1.2
ZUSAMMENFASSUNG........................................................................................................................
11
2.
INTRODUCTION.......................................................................................................................................14
2.1 RHEUMATOID ARTHRITIS (R A
)..............................................................................................................14
2.1.1 RISK FACTORS FOR R A
...............................................................................................................
14
2.1.2 JOINT DESTRUCTION IN R A
........................................................................................................
17
2.2
BONE...................................................................................................................................................18
2.2.1 BONE C E LLS
...............................................................................................................................
19
2.2.2 BONE FORMATION AND
REMODELING.........................................................................................24
2.2.3 THE INFLUENCE OF THE IMMUNE SYSTEM ON BONE M ETABOLISM
.......................................
27
2.2.4 BONE METABOLISM IN R A
.......................................................................................................
28
2.3 SYNOVITIS AND FIBROBLAST LIKE SYNOVIOCYTES (F L S
)...................................................................30
2.3.1 INFLAMMATION OF THE
SYNOVIUM.............................................................................................30
2.3.2 FIBROBLAST LIKE SYNOVIOCYTES (FLS) IN R A
........................................................................
31
2.4 TN F-A IN RA AND THE HT/VF-ATG MOUSE AS A MODEL ORGANISM
..........................................35
2.4.1 TN F-A IN R A
............................................................................................................................35
2.4.2 THE HTAF-ARTG MOUSE
MODEL..............................................................................................36
2.5 RA TREATMENT AND
NON-RESPONDERS.............................................................................................37
2.6 IONIZING RADIATION (IR) AND LOW-DOSE RADIO THERAPY (L D -R T )
...............................................
39
2.6.1 IONIZING
RADIATION...................................................................................................................
39
2.6.2 CELLULAR EFFECTS OF IR
.............................................................................................................
41
2.6.3 L D -R T
......................................................................................................................................
43
2.6.4 MOLECULAR MECHANISMS OF L D -R T
.....................................................................................
45
2.6.5 LD-RT IN ANIMAL
MODELS......................................................................................................
47
2.6 AIM OF THE
THESIS............................................................................................................................48
3. MATERIAL AND
METHODS...................................................................................................................
49
3.1
MATERIALS........................................................................................................................................
49
3.1.1 C HEM
ICALS................................................................................................................................49
3.1.2 CELL CULTURE MATERIALS AND
ADDITIVES.................................................................................
50
3.1.3 ENZYMES AND
CYTOKINES.......................................................................................................51
3.1.4 AUXILIARY M
ATERIALS..................................................................................................................52
3.1.5
INSTRUMENTS..............................................................................................................................53
3.1.6 ANTIBODIES AND
OLIGONUCLEOTIDES.......................................................................................
54
3.1.6.1 ANTIBODIES AND
ISOTYPES...................................................................................................
54
3.1.6.2
OLIGONUCLEOTIDES................................................................................................................
54
3.1.7 COMMERCIALIZED TEST SYSTEMS AND
ELISAS....................................................................56
3.1.8 M IC E
...........................................................................................................................................57
3.1.9
SOFTWARE....................................................................................................................................57
3.2 BUFFER AND
SOLUTIONS......................................................................................................................
58
3.2.1 CELL CULTURE M
EDIA..................................................................................................................58
3.2.2. BUFFER AND
SOLUTIONS..............................................................................................................59
3.2 M ETHO DS
...............................
,
..........................................................................................................62
3.2.1 ANIMAL EXPERIM
ENTS..............................................................................................................62
3.2.2 HISTOLOGY AND HISTOMORPHOMETRY OF MURINE
BONES........................................................64
3.2.3 CELL ISOLATION FROM MURINE TISSUE AND IN VITRO EXPERIM ENTS
.........................................
65
3.2.4 HUMAN RA AND OA FLS
CULTURES.................................................................................
:....68
3.2.5. FLOW CYTOMETRY ANALYSIS (F A C S
)........................................................................................
70
3.2.6 NUCLEIC-ACID BASED M
ETHODS..............................................................................................
70
3.2.7 ENZYME LINKED IMMUNOSORBENT ASSAY (E L IS A )
...........................................................
73
3.2.8 EX VIVO
IRRADIATION...................................................................................................................73
3.2.9 STATISTICAL
ANALYSIS.................................................................................................................
74
4.
RESULTS.............................................................................................................................................
75
4.1 HT N F-A TG MOUSE-DERIVED FLS DEMONSTRATE AN INFLAMMATORY
PHENOTYPE...................77
4.1.1 INFLAMMATORY FLS LINES GROW FASTER THAN NON-INFLAMMATORY F L S
..............................
77
4.1.2 HTN F-A TG MOUSE-DERIVED FLS LINES SHOW HIGHER PURITY THAN THOSE
DERIVED
FROM C57BI/6 M
ICE.................................................................................................................
79
4.1.3 HTN F-A TG MICE-DERIVED FLS SECRETE HIGH AMOUNTS OF
PRO-INFLAMMATORY
CYTOKINES.................................................................................................................................
81
4. 2 X-RAYS ADMINISTERED AT LOW DOSES MODULATES THE PHENOTYPE OF MURINE
F L S
.................
82
4.2.1 LD-RT INDUCES APOPTOSIS IN INFLAMMATORY F L S
..............................................................82
4.2.2 LD-RT HAS NO INFLUENCE ON FLS
MIGRATION......................................................................85
4.2.3 LD-RT INFLUENCES CYTOKINE SECRETION DEPENDENT ON THE INFLAMMATORY
BACKGROUND OF F L S
................................................................................................................86
4.2.4 LD-RT MODIFIES THE EXPRESSION OF CARTILAGE DESTRUCTIVE MOLECULES
IN RELIANCE
OF THE INFLAMMATORY STATU
S...................................................................................................90
4.3 LD-RT HAS AN IMPACT ON HUMAN RA- AND OA-DERIVED F L S
................................................93
4.3.1 X-RAYS REDUCE THE NUMBERS OF HUMAN RA AND OA FLS IN A DOSE
DEPENDENT
M
ANNER.....................................................................................................................................
93
4.3.2 LD-RT HAS DIVERGENT EFFECTS ON CYTOKINE RELEASE IN RA- AND O A -F
L S ....................96
4.4 LD-RT MODULATES OSTEOCLAST DIFFERENTIATION DEPENDENT UPON THEIR
INFLAMMATORY
BACKGROUND......................................................................................................................................
98
4.4.1 X-RAYS HAVE CONTRARY EFFECTS ON OSTEOCLAST DIFFERENTIATION
DEPENDING ON THEIR
INFLAMMATORY
BACKGROUND....................................................................................................98
4.4.2 IRRADIATION WITH LOW DOSES OF X-RAYS ALTERS OSTEOCLAST GENE
EXPRESSION
PROFILES DEPENDENT ON THEIR INFLAMMATORY STATU
S......................................................... 100
4.5 LD-RT INCREASES THE BONE FORMING PROPERTIES OF
OSTEOBLASTS...........................................103
4.5.1 LOW DOSES OF X-RAYS INCREASE OSTEOBLASTIC MINERALIZATION A RE A S
...........................
103
4.5.2 LD-RT TEMPORARILY INCREASES OPG SECRETION IN OSTEOBLASTS
...................................
105
4.5.3 LD-RT ALTERS THE EXPRESSION LEVELS OF OSTEOBLAST-RELATED G E N E S
............................
106
4.6 ESTABLISHMENT OF AN IN VIVO IRRADIATION SET-UP
.......................................................................
108
4.7 LD-RT IMPROVES THE COURSE OF DISEASE IN RHEUMATIC
ANIMALS......................................110
4.7.1 LD-RT IMPROVES GRIP STRENGTH AND REDUCES TN F-A LEVELS IN
TRANSGENIC
ANIMALS...................................................................................................................................110
4.7.3 A SINGLE DOSE OF 0.5GY REDUCES INFLAMMATION AND BONE EROSION IN
THE PAW
.......
112
4.7.4 LD-RT HAS NO SIGNIFICANT IMPACT ON BONE TURNOVER CLOSE TO THE
IRRADIATED
AREA.........................................................................................................................................114
4.7.5 LOCALLY APPLIED LD-RT IN HTN F-A TG ANIMALS RESULTS IN LOCAL AND
SYSTEMIC
EFFECTS....................................................................................................................................
116
5.
DISCUSSION......................................................................................................................................
118
5.1 LD-RT REDUCES THE INFLAMMATORY PHENOTYPE OF HTN F-A TG DERIVED FL S
.........................
118
5.2 LD-RT HAS AN IMPACT ON HUMAN RA AND OA-DERIVED FLS THROUGH A
REDUCTION OF
CELL
NUMBERS...................................................................................................................................120
5.3 LD-RT REDUCES OC
NUMBERS.....................................................................................................121
5.4 0.5G Y OF X-RAYS INCREASES OSTEOBLAST
ACTIVITY........................................................................122
5.4 LD-RT IMPROVES COURSE OF DISEASE THROUGH SYSTEMIC AND LOCAL EFFECTS
.........................
122
5.5 CONCLUDING REMARKS AND
OUTLOOK.............................................................................................
124
6.
REFERENCES.....................................................................................................................................127
7. A
PPENDIX........................................................................................................................................
138
7.1 TABLES AND
FIGURES......................................................................................................................
138
7.1.1 T A B LE S
.....................................................................................................................................138
7.1.2
FIGURES....................................................................................................................................139
7.2 LIST OF
ABBREVIATIONS....................................................................................................................
141
7.3 ACKNOWLEDGEMENTS
.........................
144
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| spelling | Deloch, Lisa Verfasser aut The impact of low-dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem vorgelegt von Lisa Janina Deloch aus Nürnberg Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel Erlangen ; Nürnberg [2017] 145 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Friedrich-Alexander-Universität Erlangen-Nürnberg 2017 Knochenstoffwechsel (DE-588)4216200-2 gnd rswk-swf Knochen (DE-588)4128031-3 gnd rswk-swf Antiphlogistikum (DE-588)4123144-2 gnd rswk-swf Bestrahlung (DE-588)4144952-6 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Bestrahlung (DE-588)4144952-6 s Knochen (DE-588)4128031-3 s Antiphlogistikum (DE-588)4123144-2 s Knochenstoffwechsel (DE-588)4216200-2 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029947464&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Deloch, Lisa The impact of low-dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem Knochenstoffwechsel (DE-588)4216200-2 gnd Knochen (DE-588)4128031-3 gnd Antiphlogistikum (DE-588)4123144-2 gnd Bestrahlung (DE-588)4144952-6 gnd |
| subject_GND | (DE-588)4216200-2 (DE-588)4128031-3 (DE-588)4123144-2 (DE-588)4144952-6 (DE-588)4113937-9 |
| title | The impact of low-dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem |
| title_alt | Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel |
| title_auth | The impact of low-dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem |
| title_exact_search | The impact of low-dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem |
| title_full | The impact of low-dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem vorgelegt von Lisa Janina Deloch aus Nürnberg |
| title_fullStr | The impact of low-dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem vorgelegt von Lisa Janina Deloch aus Nürnberg |
| title_full_unstemmed | The impact of low-dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem vorgelegt von Lisa Janina Deloch aus Nürnberg |
| title_short | The impact of low-dose irradiation on attenuation of inflammation and bone metabolism |
| title_sort | the impact of low dose irradiation on attenuation of inflammation and bone metabolism osteoimmunological analyses with htnf α tg and c57bi 6 mice as a model system der einfluss niedrig dosierter strahlung auf die abmilderung von entzundungsprozessen und knochenstoffwechsel osteoimmunologische untersuchungen mit den htnf α tg und c57bi 6 mausstammen als modellsystem |
| title_sub | osteoimmunological analyses with hTNF-α tg and C57BI/6 mice as a model system = Der Einfluss Niedrig Dosierter Strahlung auf die Abmilderung von Entzündungsprozessen und Knochenstoffwechsel : Osteoimmunologische Untersuchungen mit den hTNF-α tg und C57BI/6 Mausstämmen als Modellsystem |
| topic | Knochenstoffwechsel (DE-588)4216200-2 gnd Knochen (DE-588)4128031-3 gnd Antiphlogistikum (DE-588)4123144-2 gnd Bestrahlung (DE-588)4144952-6 gnd |
| topic_facet | Knochenstoffwechsel Knochen Antiphlogistikum Bestrahlung Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029947464&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT delochlisa theimpactoflowdoseirradiationonattenuationofinflammationandbonemetabolismosteoimmunologicalanalyseswithhtnfatgandc57bi6miceasamodelsystemdereinflussniedrigdosierterstrahlungaufdieabmilderungvonentzundungsprozessenundknochenstoffwechselosteoimmunologischeu AT delochlisa dereinflussniedrigdosierterstrahlungaufdieabmilderungvonentzundungsprozessenundknochenstoffwechsel |