The impact of chronic inflammation on the growing skeleton: lessons from interleukin-6 transgenic mice

Area of Science:

• Pediatric Endocrinology
• Skeletal Biology
• Inflammation Research

Background:

• Chronic inflammatory diseases in children impair linear growth and bone accrual.
• Inflammation may directly harm the developing skeleton, independent of nutrition or medication.
• Interleukin-6 (IL-6) is implicated as a key mediator of these inflammatory effects.

Purpose of the Study:

• To review the detrimental effects of inflammation on the pediatric skeletal system.
• To explore the role of interleukin-6 (IL-6) in mediating skeletal abnormalities during chronic inflammation.
• To identify potential therapeutic targets for mitigating inflammation's impact on growing bones.

Main Methods:

• Review of existing animal and clinical data on chronic inflammation and skeletal development.
• Analysis of studies investigating interleukin-6 (IL-6) overexpression in prepubertal mice.
• Examination of growth plate, ossification, and bone cell activity in relevant models.

Main Results:

• Animal models with IL-6 overexpression exhibit stunted growth and defective skeletal development.
• Observed abnormalities include impaired insulin-like growth factor I system, growth plate defects, and delayed ossification.
• Osteoblast and osteoclast activity become uncoupled, leading to defective ossification.

Conclusions:

• The findings highlight significant tissue, cellular, and molecular abnormalities caused by inflammation.
• These abnormalities in the developing skeleton provide a basis for therapeutic interventions.
• Targeting inflammation, particularly IL-6 pathways, may correct detrimental skeletal effects in children.