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Osteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
Bingzi Dong1,2,3, Masahiro Hiasa4, Yoshiki Higa4
1Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan.
Nature Communications
|November 24, 2022
Summary
Mechanical loading of bone stimulates Interleukin-11 (IL-11) production by bone cells, which is crucial for bone formation and regulating systemic adiposity. IL-11 deficiency impairs bone
Area of Science:
- Bone Biology and Metabolism
- Endocrinology
- Metabolic Syndrome Research
Background:
- Mechanical loading of bone influences adipose tissue energy expenditure.
- Bone-derived factors may mediate communication with adipose tissue.
- Interleukin-11 (IL-11) is expressed in bone, upregulated by mechanical loading, and affects osteogenesis and adipogenesis.
Purpose of the Study:
- To investigate the role of Interleukin-11 (IL-11) in bone's response to mechanical loading.
- To determine the impact of IL-11 on systemic adiposity and glucose metabolism.
- To elucidate the cellular source of IL-11 involved in these processes.
Main Methods:
- Systemic deletion of IL-11 in mice (IL-11-/-).
- Conditional deletion of IL-11 in osteoblasts/osteocytes (osteocalcin-Cre;IL-11fl/fl) and adipocytes (adiponectin-Cre;IL-11fl/fl).
- Assessment of bone mass, bone formation, bone resorption, Wnt signaling, systemic adiposity, and glucose tolerance.
Main Results:
- Systemic IL-11 deletion reduced bone mass and blunted bone formation response to mechanical loading.
- IL-11 deficiency led to increased systemic adiposity and glucose intolerance.
- Osteoblast/osteocyte-specific IL-11 deletion mimicked systemic deletion effects, while adipocyte-specific deletion showed no abnormalities.
- Mechanical unloading-induced bone resorption was unaffected by IL-11 deletion.
Conclusions:
- Osteoblast/osteocyte-derived IL-11 is a critical mediator of bone's response to mechanical loading.
- IL-11 plays a significant role in regulating systemic adiposity and glucose metabolism.
- Targeting IL-11 may offer therapeutic potential for osteoporosis and metabolic syndromes.
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