Abstract | BACKGROUND: METHODS:
Colitis was induced in interleukin-10 knockout mice (PAC IL-10 k.o.) by peroral administration of piroxicam for 12 days. The degree of colitis was assessed by clinical, macroscopic, and microscopic evaluation. Trabecular and cortical bone microarchitecture of tibia were determined using micro-computed tomography. Moreover, the serum levels of bone formation and bone resorption biomarkers were measured, and inflammatory protein profiling was performed on colons. RESULTS: PAC IL-10 k.o. mice developed severe colitis, characterized by hyperplasia and focal transmural inflammation, which was consistent with Crohn's disease-like pathology. The gut inflammation was accompanied by a 14% and 12% reduction in trabecular thickness relative to piroxicam-treated wild type and untreated wild type mice, respectively (P < 0.001). The trabecular bone structure was also changed in PAC IL-10 k.o. mice, whereas no differences in cortical bone geometry were observed. The trabecular thickness was inversely correlated with serum levels of CTX (r = -0.93, P = 0.006). Moreover, numerous inflammatory mediators, including RANKL and osteoprotegerin, were significantly increased in the colon of PAC IL-10 k.o. mice. CONCLUSIONS: PAC IL-10 k.o. mice develop bone loss and changed trabecular structure, as a result of increased bone resorption. Thus, the PAC IL-10 k.o. model could be a useful experimental model in preclinical research of inflammatory bowel disease-associated bone loss.
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Authors | Kristine Holgersen, Ross Dobie, Colin Farquharson, Rob vanʼt Hof, Syed Faisal Ahmed, Axel Kornerup Hansen, Thomas L Holm |
Journal | Inflammatory bowel diseases
(Inflamm Bowel Dis)
Vol. 21
Issue 2
Pg. 257-66
(Feb 2015)
ISSN: 1536-4844 [Electronic] England |
PMID | 25569742
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Interleukin-10
- Piroxicam
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(toxicity)
- Bone Density
(drug effects)
- Bone Diseases, Metabolic
(etiology, pathology)
- Colitis
(chemically induced, immunology, pathology)
- Disease Models, Animal
- Female
- Inflammation
(etiology, pathology)
- Interleukin-10
(physiology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Osteoporosis
(etiology, pathology)
- Piroxicam
(toxicity)
- X-Ray Microtomography
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