Interleukin-6 signaling in osteoblasts regulates bone remodeling during exercise.

Area of Science:

• Bone Biology
• Exercise Physiology
• Endocrinology

Background:

• Aerobic exercise confers numerous health benefits, including positive effects on bone remodeling.
• The precise mechanisms by which exercise influences bone homeostasis are not fully understood.
• Interleukin-6 (IL-6) has emerged as a potential mediator in bone-muscle crosstalk during physical activity.

Purpose of the Study:

• To investigate the role of interleukin-6 (IL-6) signaling in osteoblasts in mediating the effects of aerobic exercise on bone homeostasis.
• To determine if IL-6 signaling within bone cells is essential for exercise-induced bone benefits.

Main Methods:

• Assessed the expression of IL-6 receptor (Il6r) in the bones of wild-type (WT) mice following aerobic exercise.
• Utilized a genetically modified mouse model lacking the IL-6 receptor alpha specifically in osteoblasts (Il6r_osb^-/-).
• Compared bone mass, remodeling parameters, and bone formation in sedentary and exercise-trained Il6r_osb^-/- mice versus control littermates.

Main Results:

• Aerobic exercise increased Il6r expression in WT mouse bones.
• Sedentary Il6r_osb^-/- mice exhibited normal bone mass and remodeling compared to controls.
• Exercise-trained Il6r_osb^-/- mice failed to show exercise-induced increases in bone mass and remodeling.
• Il6r_osb^-/- mice undergoing exercise displayed impaired bone formation, indicating defective osteoblast activation.

Conclusions:

• IL-6 signaling in osteoblasts is crucial for promoting high bone turnover during aerobic exercise.
• Disruption of IL-6 signaling in osteoblasts abrogates the beneficial effects of exercise on bone mass and formation.
• This study highlights a key molecular pathway through which exercise positively impacts bone health.