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Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system

De Benedetti, Fabrizio, Rucci, Nadia, Del Fattore, Andrea, Peruzzi, Barbara, Paro, Rita, Longo, Maurizio, Vivarelli, Marina, Muratori, Flaminia, Berni, Silvia, Ballanti, Paola, Ferrari, Serge, Teti, Anna·2006·Arthritis & Rheumatism
DOI 10.1002/art.22175
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Abstract

Objective: To identify the mediator responsible for the impact of chronic inflammation on skeletal development in children (bone loss, defective peak bone mass accrual, stunted growth), we evaluated the effects of chronic interleukin‐6 (IL‐6) overexpression on the skeletons of growing prepubertal mice. Methods: We studied IL‐6–transgenic mice that had high circulating IL‐6 levels since birth. Trabecular and cortical bone structure were analyzed by microcomputed tomography. Epiphyseal ossification, growth plates, and calvariae were studied by histology/histomorphometry. Osteoclastogenesis, osteoblast function/differentiation, and the effects of IL‐6 on bone cells were studied in vitro. Osteoblast gene expression was evaluated by reverse transcriptase–polymerase chain reaction. The mineral apposition rate was evaluated dynamically in cortical bone by in vivo double fluorescence labeling. Results: In prepubertal IL‐6–transgenic mice, we observed osteopenia, with severe alterations in cortical and trabecular bone microarchitecture, as well as uncoupling of bone formation from resorption, with decreased osteoblast and increased osteoclast number and activity. Increased osteoclastogenesis and reduced osteoblast activity, secondary to decreased precursor proliferation and osteoblast function, were present. IL‐6–transgenic mice also showed impaired development of growth plates and epiphyseal ossification centers. Intramembranous and endochondral ossification and the mineral apposition rate were markedly affected, showing the presence of defective ossification. Conclusion: Chronic overexpression of IL‐6 alone induces a skeletal phenotype closely resembling growth and skeletal abnormalities observed in children with chronic inflammatory diseases, pointing to IL‐6 as a pivotal mediator of the impact of chronic inflammation on postnatal skeletal development. We hypothesize that IL‐6–modifying drugs may reduce skeletal defects and prevent the growth retardation associated with these diseases.

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Metadata

Authors
De Benedetti, F., Rucci, N., Del Fattore, A., Peruzzi, B., Paro, R., Longo, M., Vivarelli, M., Muratori, F., Berni, S., Ballanti, P., Ferrari, S., & Teti, A.
Venue
Arthritis & Rheumatism
Publisher
Wiley
Published
2006-10-30
Volume
54
Issue
11
Pages
3551-3563
ISSN
  • 0004-3591
  • 1529-0131
DOI
10.1002/art.22175
Cited by
296
References
3
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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CoChat. (2026). Citation check: Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. https://app.cochat.ai/papers/10.1002/art.22175
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De Benedetti, F., Rucci, N., Del Fattore, A., Peruzzi, B., Paro, R., Longo, M., Vivarelli, M., Muratori, F., Berni, S., Ballanti, P., Ferrari, S., & Teti, A. (2006). Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. Arthritis & Rheumatism. https://doi.org/10.1002/art.22175