Animal Models in Osteoporosis Research

Kimmel, Donald B.

doi:10.1016/b978-012098652-1.50197-9

Cited by 6 publications

(5 citation statements)

References 348 publications

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“…Ovariectomy of mature mice induces cancellous and cortical bone loss in axial and appendicular sites. Since these changes mimic processes observed in postmenopausal women (15), this model has been widely used to study etiology of osteoporosis (9). In this study, we identified genes that are altered following OVX and could account for observed bone loss.…”

Section: Discussionmentioning

confidence: 84%

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Gene Expression Profiling in Bone Tissue of Osteoporotic Mice

Orlić¹,

Borovečki²,

Šimić³

et al. 2007

Archives of Industrial Hygiene and Toxicology

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Ovaricetomized (OVX) animals represent an optimal model to investigate bone loss in osteoporosis. To further elucidate the underlying mechanisms of decreased bone formation and increased bone resorption following OVX, we conducted gene expression profiling experiments using bone samples of ovariectomized C57BL/6J mice. Following OVX, genes involved in immune response, cell cycle regulation, growth, apoptosis and bone resorption were upregulated, while genes that are important for regular cell processes, mitosis, metabolism of carbohydrates, extracellular matrix structure, angiogenesis, skeletal development and morphogenesis were downregulated. Among bone specific genes we observed upregulation of interleukin 7 (IL-7), IL-7 receptor and matrix metallopeptidase 8, while genes such as transforming growth factor-beta 3, procollagen type I and procollagen type VI exhibited marked decrease in expression. We also observed downregulation of two genes, parathyroid hormone receptor 1 and WD repeat domain 5, that are involved in skeletal development but were not previously reported to be altered in osteoporosis. We further performed gene set enrichment analysis (GSEA) in order to calculate enrichment of pathways specifically altered in murine bones following ovariectomy. In conclusion, OVX greatly influences expression of various genes involved in diverse biological processes confirming the notion that numerous pathways play an important role in pathophysiology of osteoporosis.

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Section: Discussionmentioning

confidence: 84%

“…Ovariectomized (OVX) animals represent an optimal animal model to investigate bone loss in osteoporosis (9). Previous gene expression profiling experiments performed on femurs of OVX and vehicle-treated rats, revealed a specific profile of 644 differentially expressed genes when compared to sham control rats (10).…”

mentioning

confidence: 99%

Gene Expression Profiling in Bone Tissue of Osteoporotic Mice

Orlić¹,

Borovečki²,

Šimić³

et al. 2007

Archives of Industrial Hygiene and Toxicology

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“…Rats and rabbits are the most commonly used small animals in dental implantology (Dereka et al, 2018;Stadlinger et al, 2012b). In rats, symptoms of postmenopausal osteoporosis can be induced by ovariectomy with well-known phenotypic consequences of strongly enhanced osteoclastic bone resorption (Kimmel, 2002;Komori 2015). The distribution of implant sites was also analysed by Stadlinger et al (2012b).…”

Section: Limitations Of the Studymentioning

confidence: 99%

Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model

Korn¹,

Krämer²,

Schlottig³

et al. 2019

eCM

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Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle, versus sole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model. Uncoated reference surface implants or ZOL-coated implants (n = 64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation by ex vivo µCT, histology and biomechanical testing. Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants. In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.

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“…We selected tenweek-old C57BL/6 mice for several reasons. First, this strain is used widely for the generation of transgenic and knockout animals for bone research 24 . In particular, numerous genetic variants are available, making these animals a useful tool for studying the molecular and cellular mechanisms underlying osseointegration.…”

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confidence: 99%