Bone remodeling in experimental enthesitis: = Knochenumbau in experimenteller Enthesitis
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Erlangen ; Nürnberg
[2019]
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Physical Description: | 147 Seiten Illustrationen, Diagramme 30 cm |
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MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV045551015 | ||
| 003 | DE-604 | ||
| 005 | 20191024 | ||
| 007 | t | ||
| 008 | 190409s2019 gw a||| m||| 00||| eng d | ||
| 016 | 7 | |a 1182488749 |2 DE-101 | |
| 020 | |c Broschur | ||
| 035 | |a (OCoLC)1104934152 | ||
| 035 | |a (DE-599)DNB1182488749 | ||
| 040 | |a DE-604 |b ger |e rda | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c XA-DE | ||
| 049 | |a DE-29T |a DE-29 |a DE-355 | ||
| 084 | |a 570 |2 sdnb | ||
| 084 | |a 610 |2 sdnb | ||
| 100 | 1 | |a Schulze-Zachau, Christine |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Bone remodeling in experimental enthesitis |b = Knochenumbau in experimenteller Enthesitis |c vorgelegt von Christine Schulze-Zachau |
| 246 | 1 | 3 | |a Knochenumbau in experimenteller Enthesitis |
| 246 | 1 | 1 | |a Knochenumbau in experimenteller Enthesitis |
| 264 | 1 | |a Erlangen ; Nürnberg |c [2019] | |
| 300 | |a 147 Seiten |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Friedrich-Alexander-Universität Erlangen-Nürnberg |d 2019 | ||
| 650 | 0 | 7 | |a Knochenumbau |0 (DE-588)4264191-3 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Arthritis |0 (DE-588)4068867-7 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Tiermodell |0 (DE-588)4140660-6 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Enthesiopathie |0 (DE-588)1084036398 |2 gnd |9 rswk-swf |
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 689 | 0 | 0 | |a Tiermodell |0 (DE-588)4140660-6 |D s |
| 689 | 0 | 1 | |a Knochenumbau |0 (DE-588)4264191-3 |D s |
| 689 | 0 | 2 | |a Arthritis |0 (DE-588)4068867-7 |D s |
| 689 | 0 | 3 | |a Enthesiopathie |0 (DE-588)1084036398 |D s |
| 689 | 0 | |5 DE-604 | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u http://d-nb.info/1182488749/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030934993&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-030934993 | ||
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| _version_ | 1804179525870813184 |
|---|---|
| adam_text | TABLE
OF
CONTENT
1
ABSTRACT
..................................................................................................................
-
6
-
2
ZUSAMMENFASSUNG
...............................................................................................
-
8
-
3
INTRODUCTION
...........................................................................................................
-10-
3.1
BONE
..............................................................................................................
-10-
3.1.1
BONE
STRUCTURE
AND
FUNCTION
.........................................................................
-10
-
3.1.2
BONE
CELLS
..................................................................................................
-11-
3.1.2.1
OSTEOBLASTS
DIFFERENTIATION
AND
MINERALIZATION
......................................
-11-
3.1.2.2
OSTEOCLAST
DIFFERENTIATION
AND
RESORPTION
..............................................
-13
-
3.1.2.3
OSTEOCYTES
...........................................................................................
-15-
3.1.3
BONE
REMODELING
........................................................................................
-17-
3.1.3.1
RANKL/OPG
SYSTEM
.............................................................................
-17-
3.1.3.2
OXIDATIVE
STRESS
IN
BONE
REMODELING....................................................
-18
-
3.2
OSTEOIMMUNOLOGY
-
THE
INTERACTION
OF
IMMUNE
SYSTEM
AND
BONE
........
-
21
-
3.3
INFLAMMATORY
ARTHRITIS
.................................................................................
-
22
-
3.3.1
EXAMPLES
OF
INFLAMMATORY
ARTHRITIS..............................................................
-
22
-
3.3.1.1
RHEUMATOID
ARTHRITIS
.............................................................................
-
22
-
3.3.1.2
GOUT
......................................................................................................
-23-
3.3.1.3
SPONDYLOARTHROPATHIES
(SPA)
...............................................................
-
24
-
3.3.2
ENTHESITIS
-
HALLMARK
OF
INFLAMMATORY
ARTHRITIS............................................
-
25
-
3.3.3
TREATMENT
OF
INFLAMMATORY
ARTHRITIDES
........................................................
-
26
-
3.3.4
IMAGING
OF
INFLAMMATORY
ARTHRITIS
BY
(DCE)-MRI
AND
PET-CT
....................
-
28
-
3.3.4.1
(DCE)-MRI
...........................................................................................
-28-
3.3.4.2
PET-CT
.................................................................................................
-30-
3.4
MSU
CRYSTALS
IN
IMMUNITY
AND
INFLAMMATION
...........................................
-
31
-
3.4.1
MSU
MEDIATED
CELL
ACTIVATION
....................................................................
-
31
-
3.4.2
INTERACTION
OF
MSU
CRYSTALS
AND
NEUTROPHILS
..............................................
-
33
-
3.4.2.1
ROLE
OF
NEUTROPHILS
IN
IMMUNITY
............................................................
-
33
-
3.4.2.2
NEUTROPHIL
EXTRACELLULAR
TRAPS
(NETS)
AND
NET
FORMATION
...................
-
34
-
3.4.2.3
MSU-INDUCED
NET
FORMATION
AND
INFLAMMATION..................................
-
35
-
3.5
ROS
-
THE
MOLECULAR
BASIS
OF
NET
FORMATION
.........................................
-
37
-
3.5.1
ROS
PRODUCTION
BY
THE
NOX2
COMPLEX
.....................................................
-
37
-
3.5.2
A
ROS-DEFICIENT
MOUSE
MODEL
MIMICKING
INFLAMMATORY
ARTHRITIS
................
-
38
-
4
AIM
.........................................................................................................................
-40
-
5
MATERIAL
.................................................................................................................
-41
-
5.1
ANIMALS
..........................................................................................................
-41-
-1
-
5.2
ANTIBODIES
....................................................................................................
-
41
-
5.3
BUFFERS
AND
SOLUTIONS
...................................................................................
-42-
5.4
CELL
CULTURE
..................................................................................................
-
43
-
5.5
CHEMICALS,
PROTEINS
AND
REAGENTS
.............................................................
-
44
-
5.6
CONSUMABLE
MATERIAL
................................................................................
-
45
-
5.7
DEVICES
.......................................................................................................
-
46
-
5.8
KITS
...............................................................................................................
-47
-
5.9
Q-RT
PRIMER
.................................................................................................
-
47
-
5.10
TAQMAN
PRIMERS
AND
PROBES
......................................................................
-48-
5.11
SOFTWARE
.......................................................................................................
-48-
6
METHODS
..................................................................................................................
-
49
-
6.1
PREPARATION
OF
MSU
CRYSTALS
.......................................................................
-
49
-
6.2
MEASUREMENT
OF
ROS
PRODUCTION
..............................................................
-
49
-
6.3
ANIMAL
EXPERIMENTS
.....................................................................................
-
49
-
6.3.1
MONOSODIUM
URATE
CRYSTAL-INDUCED
ENTHESITIS
.............................................
-
50
-
6.3.2
TREATMENT
OF
MSU-INDUCED
ENTHESITIS
.........................................................
-
50
-
6.3.3
HIND
LIMB
UNLOADING
.....................................................................................
-
51
-
6.4
PREPARATION
OF
MICE
.....................................................................................
-
51
-
6.5
GENOTYPING
...................................................................................................
-
52
-
6.5.1
ISOLATION
OF
GDNA
........................................................................................
-52-
6.5.2
TAQMAN
GENOTYPING
ASSAY
BY
AB
I
...............................................................
-
52
-
6.6
BONE
ANALYSES
.............................................................................................
-
53
-
6.6.1
PCT
IMAGING................................................................................................
-53-
6.6.2
MULTIMODAL
LONGITUDINAL
IMAGING
..................................................................
-
53
-
6.6.2.1
(DCE-)MR
IMAGING
AND
ANALYIS
............................................................
-
53
-
6.6.2.2
PET/CT
IMAGING
...................................................................................
-
54
-
6.7
ANALYSIS
OF
INFLAMMATORY
INFILTRATES
.............................................................
-
54
-
6.7.1
COLLAGENASE
DIGESTION
OF
HIND
PAWS
............................................................
-
54
-
6.7.2
FLOW
CYTOMETRY
............................................................................................
-
55
-
6.7.2.1
CELLULAR
COMPOSITION
OF
INFLAMMATORY
INFILTRATES
....................................
-
55
-
6.7.2.2
VERIFICATION
OF
NEUTROPHIL
DEPLETION
........................................................
-
55
-
6.8
METHODS
TO
STUDY
RNA
...............................................................................
-
56
-
6.8.1
RNA
ISOLATION
.............................................................................................
-56-
6.8.2
DNASE
DIGESTION
AND
CDNA
SYNTHESIS
.......................................................
-
56
-
6.8.3
QUANTITATIVE
REAL-TIME
PCR
.........................................................................
-
57
-
6.8.4
GENOME
SEQUENCING
..................................................................................
-
57
-
-2-
6.9
HISTOLOGY
......................................................................................................
-58-
6.9.1
PARAFFIN........................................................................................................
-58-
6.9.1.1
H&E
STAINING
.........................................................................................
-58-
6.9.1.2
TRAP
STAINING
.......................................................................................
-59-
6.9.1.3
SAFRANIN-0
STAINING
...............................................................................
-59-
6.9.1.4
TOLUIDINE
BLUE
STAINING...........................................................................
-
59
-
6.9.2
METHACRYLATE
...............................................................................................
-
60
-
6.10
IMMUNOHISTOLOGY
.........................................................................................
-60-
6.10.1
ANGIOGENESIS
AND
LY6G
+
NEUTROPHIL
PRESENCE
...........................................
-
60
-
6.10.2
COLLAGEN
TYPE
I
AND
COLLAGEN
TYPE
X
..........................................................
-
61
-
6.11
ANALYSIS
OF
BONE
FORMATION
AND
RESORPTION
IN
VIVO
...................................
-
61
-
6.11.1
COLLECTING
SERUM
SAMPLES
.........................................................................
-
61
-
6.11.2
IN
VIVO
CALCEIN
LABELING
AND
DETERMINATION
OF
MS/BS
.................................
-
61
-
6.11.3
DETERMINATION
OF
BONE
DESTRUCTIVE
MARKER
IN
SERUM....................................
-
62
-
6.12
CELL
CULTURE
EXPERIMENTS
.............................................................................
-
62
-
6.12.1
OSTEOBLASTS
.................................................................................................
-62-
6.12.1.1
OSTEOBLAST
CULTIVATION
..........................................................................
-
62
-
6.12.1.2
OSTEOBLAST
DIFFERENTIATION.....................................................................
-
63
-
6.12.1.3
OSTEOBLAST
MINERALIZATION
....................................................................
-
63
-
6.12.2
OSTEOCLASTS
.................................................................................................
-
64
-
6.12.2.1
OSTEOCLAST
CULTIVATION
AND
DIFFERENTIATION
.............................................
-
64
-
6.12.2.2
OSTEOCLAST
RESORPTION
..........................................................................
-
64
-
6.13
STATISTICAL
ANALYSIS
.................................................................................
-64-
7
RESULTS
...................................................................................................................
-
65
-
7.1
IDENTIFYING
AND
CHARACTERIZING
BALB/C
.NCF1**
MICE
...............................
-
65
-
7.2
INTEROSSEAL
SUBCUTANEOUS
MSU
CRYSTAL
INJECTION
RESULTS
IN
SUSTAINED
PAW
SWELLING
IN
BALB/C.A/CF7**
MICE
................................................................
-
66
-
7.3
MSU-INJECTION
CAUSES
ENTHESITIS
AND
NEW
BONE
FORMATION
IN
BALB/C.
NCF1**
MICE
.............................................................................................................
-67
-
7.4
HIGH
OSTEOBLAST
ACTIVITY
SUPPORTS
ENTHESIOPHYTE
FORMATION
....................
-
70
-
7.5
MSU-INDUCED
ENTHESITIS
INCREASES
NEW
BONE
FORMING
ACTIVITY
IN
BALB/C./VCFT**
MICE
...................................................................................
-71
-
7.6
HON-INVASIVE
ANALYSIS
OF
MSU-INDUCED
ENTHESIOPHYTES
........................
-
73
-
7.7
ENTHESIOPHYTES
ARISE
DUE
TO
INTRAMEMBRANOUS
OSSIFICATION
PROCESSES
-
74
-
7.8
DEFICIENT
NOX2-DERIVED
ROS
PRODUCTION
DOES
NOT
IMPACT
OSTEOBLAST
DIFFERENTIATION
..............................................................................................
-
76
-
7.9
ALKALINE
PHOSPHATASE
PLAYS
A
MINOR
ROLE
IN
THE
FORMATION
OF
ENTHESIOPHYTES
......................................................................................................................
-77-
-3-
7.10
SUSTAINED
ENTHESITIS
CAUSES
BONE
DESTRUCTION
-
78
-
7.11
DEFICIENT
NOX2-DERIVED
ROS
PRODUCTION
DOES
NOT
IMPACT
OSTEOCLASTOGENESIS
-
80
-
7.12
DEFICIENT
NOX2-DERIVED
ROS
PRODUCTION
DOES
NOT
HAVE
A
STRIKING
IMPACT
ON
BONE
RESORPTION
-
82
-
7.13
MSU-INDUCED
ENTHESITIS
INDUCES
CHRONIC
INFLAMMATION
IN
BALB/C./VCFF
**
MICE
-
84
-
7.14
MSU-INDUCED
ENTHESITIS
INCREASES
VASCULARIZATION
AND
BLOOD
FLOW
IN
AFFECTED
BALB/C
.NCF1**
MICE
PAWS
-
85
-
7.15
CELLULAR
BASIS
OF
INFLAMMATORY
TISSUE
IN
MSU-INDUCED
ENTHESITIS
-
89
-
7.16
NEUTROPHILS
DRIVE
MSU-INDUCED
ENTHESITIS
AND
IMPACT
NEW
BONE
FORMATION
.
-92-
7.17
UNLOADING
PREVENTS
MSU-INDUCED
NEW
BONE
FORMATION
-
94
-
7.18
COLCHICINE
TREATMENT
ATTENUATES
MSU-INDUCED
ENTHESITIS
AT
EARLY
STAGES....
-96-
7.19
NEITHER
TNF
NOR
IL-17A/F,
IL-23
OR
IL-1
IMPACTS
MSU-INDUCED
ENTHESITIS
AND
NEW
BONE
FORMATION
-
98
-
7.20
CONTROVERSIAL
RESULTS
CONCERNING
IL-6
DEPLETION
IN
MSU-INDUCED
ENTHESITIS
AND
NEW
BONE
FORMATION
-100
-
7.21
PROSTAGLANDINS
INFLUENCE
MSU-INDUCED
ENTHESITIS
AND
NEW
BONE
FORMATION
-102-
8
DISCUSSION
-105-
8.1
MSU
CRYSTALS
AS
A
SUITABLE
TRIGGER
OF
EXPERIMENTAL
ENTHESITIS
AND
NEW
BONE
FORMATION
-105
-
8.2
A
MOUSE
MODEL
SUITABLE
TO
ANALYSE
CHRONIC
EXPERIMENTAL
ENTHESITIS
AND
NEW
BONE
FORMATION
-106
-
8.3
INFLAMMATORY
AND
OSSIFICATION
CHANGES
DUE
TO
LOCAL
MSU-INJECTION....
-107
-
8.4
CHARACTERIZATION
AND
FORMATION
OF
THE
ENTHESIOPHYTE
-108
-
8.5
CELLULAR
BASIS
OF
ENTHESIOPHYTE
FORMATION
-109
-
8.5.1
OSTEOCLASTS
-109
-
8.5.2
OSTEOBLASTS
-110-
8.6
MULTIMODAL
IMAGING
AS
A
VALUABLE
TOOL
TO
ANALYSE
ENTHESITIS
AND
NEW
BONE
FORMATION
-112-
8.7
MULTIMODAL
ASSESSMENT
OF
EXPERIMENTAL
ENTHESITIS
AND
NEW
BONE
FORMATION
-114-
8.7.1
ASSESSMENT
OF
BONE
FORMING
ACTIVITY
IN
MSU-INDUCED
ENTHESITIS
-114-
8.7.2
ASSESSMENT
OF
BONE
EROSIONS
IN
MSU-INDUCED
ENTHESITIS
-115-
8.7.3
ASSESSMENT
OF
INFLAMMATION
AND
VASCULARIZATION
IN
MSU-INDUCED
ENTHESITIS
-115-
-4-
8.8
CHARACTERIZATION
OF
MSU-INDUCED
INFLAMMATORY
TISSUE
.........................
-117-
8.9
TREATMENTS
TO
COUNTERACT
EXPERIMENTAL
ENTHESITIS
AND
NEW
BONE
FORMATION.
-118-
8.9.1
NEUTROPHILS
..............................................................................................
-118-
8.9.2
WEIGHT
BEARING
........................................................................................
-119-
8.9.3
COLCHICINE
................................................................................................
-119-
8.9.4
ANAKINRA
...................................................................................................
-120-
8.9.5
IL-17A/F
AND
IL-23
AS
THE
MAIN
CYTOKINES
DRIVING
ENTHESITIS
.....................
-121
-
8.9.6
TNF
AND
IL-6
AS
THE
MAIN
CYTOKINES
DRIVING
BONE
RESORPTION
....................
-122
-
8.9.7
INDOMETACIN
.............................................................................................
-123
-
8.10
CONCLUDING
REMARKS
................................................................................
-124
-
9
ABBREVIATIONS
....................................................................................................
-127
-
10
REFERENCES
.........................................................................................................
-131-
-5-
|
| any_adam_object | 1 |
| author | Schulze-Zachau, Christine |
| author_facet | Schulze-Zachau, Christine |
| author_role | aut |
| author_sort | Schulze-Zachau, Christine |
| author_variant | c s z csz |
| building | Verbundindex |
| bvnumber | BV045551015 |
| ctrlnum | (OCoLC)1104934152 (DE-599)DNB1182488749 |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV045551015 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T08:21:15Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-030934993 |
| oclc_num | 1104934152 |
| open_access_boolean | |
| owner | DE-29T DE-29 DE-355 DE-BY-UBR |
| owner_facet | DE-29T DE-29 DE-355 DE-BY-UBR |
| physical | 147 Seiten Illustrationen, Diagramme 30 cm |
| publishDate | 2019 |
| publishDateSearch | 2019 |
| publishDateSort | 2019 |
| record_format | marc |
| spelling | Schulze-Zachau, Christine Verfasser aut Bone remodeling in experimental enthesitis = Knochenumbau in experimenteller Enthesitis vorgelegt von Christine Schulze-Zachau Knochenumbau in experimenteller Enthesitis Erlangen ; Nürnberg [2019] 147 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Friedrich-Alexander-Universität Erlangen-Nürnberg 2019 Knochenumbau (DE-588)4264191-3 gnd rswk-swf Arthritis (DE-588)4068867-7 gnd rswk-swf Tiermodell (DE-588)4140660-6 gnd rswk-swf Enthesiopathie (DE-588)1084036398 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Tiermodell (DE-588)4140660-6 s Knochenumbau (DE-588)4264191-3 s Arthritis (DE-588)4068867-7 s Enthesiopathie (DE-588)1084036398 s DE-604 B:DE-101 application/pdf http://d-nb.info/1182488749/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030934993&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Schulze-Zachau, Christine Bone remodeling in experimental enthesitis = Knochenumbau in experimenteller Enthesitis Knochenumbau (DE-588)4264191-3 gnd Arthritis (DE-588)4068867-7 gnd Tiermodell (DE-588)4140660-6 gnd Enthesiopathie (DE-588)1084036398 gnd |
| subject_GND | (DE-588)4264191-3 (DE-588)4068867-7 (DE-588)4140660-6 (DE-588)1084036398 (DE-588)4113937-9 |
| title | Bone remodeling in experimental enthesitis = Knochenumbau in experimenteller Enthesitis |
| title_alt | Knochenumbau in experimenteller Enthesitis |
| title_auth | Bone remodeling in experimental enthesitis = Knochenumbau in experimenteller Enthesitis |
| title_exact_search | Bone remodeling in experimental enthesitis = Knochenumbau in experimenteller Enthesitis |
| title_full | Bone remodeling in experimental enthesitis = Knochenumbau in experimenteller Enthesitis vorgelegt von Christine Schulze-Zachau |
| title_fullStr | Bone remodeling in experimental enthesitis = Knochenumbau in experimenteller Enthesitis vorgelegt von Christine Schulze-Zachau |
| title_full_unstemmed | Bone remodeling in experimental enthesitis = Knochenumbau in experimenteller Enthesitis vorgelegt von Christine Schulze-Zachau |
| title_short | Bone remodeling in experimental enthesitis |
| title_sort | bone remodeling in experimental enthesitis knochenumbau in experimenteller enthesitis |
| title_sub | = Knochenumbau in experimenteller Enthesitis |
| topic | Knochenumbau (DE-588)4264191-3 gnd Arthritis (DE-588)4068867-7 gnd Tiermodell (DE-588)4140660-6 gnd Enthesiopathie (DE-588)1084036398 gnd |
| topic_facet | Knochenumbau Arthritis Tiermodell Enthesiopathie Hochschulschrift |
| url | http://d-nb.info/1182488749/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=030934993&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT schulzezachauchristine boneremodelinginexperimentalenthesitisknochenumbauinexperimentellerenthesitis AT schulzezachauchristine knochenumbauinexperimentellerenthesitis |
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