Interleukin-11 receptor signaling is required for normal bone remodeling

Area of Science:

• Bone Biology
• Endocrinology
• Immunology

Background:

• Interleukin (IL)-6 and -11 are cytokines that influence bone metabolism and are implicated in bone loss associated with estrogen deficiency.
• Both cytokines share the gp130 co-receptor, suggesting linked roles and potential compensation mechanisms in maintaining bone homeostasis.

Purpose of the Study:

• To investigate the in vivo roles of IL-11 and IL-6 signaling in bone turnover and trabecular bone mass.
• To determine if IL-11 signaling is necessary for the skeletal effects of estrogen deficiency and estradiol treatment.

Main Methods:

• Examined the bone phenotype of IL-11 receptor alpha knockout (IL-11Ralpha1-/-) mice, IL-6 knockout (IL-6-/-) mice, and double knockout mice.
• Assessed ovariectomized IL-11Ralpha1-/- mice treated with estradiol to evaluate estrogen's effects.

Main Results:

• IL-11Ralpha1-/- mice exhibited significantly higher trabecular bone volume, reduced bone resorption, and decreased bone formation compared to wildtype controls.
• Osteoclast differentiation was suppressed in IL-11Ralpha1-/- precursors, while osteoblast generation was not significantly altered.
• IL-6 deficiency alone did not affect bone turnover, and the absence of both IL-6 and IL-11Ralpha signaling resulted in a phenotype identical to IL-11Ralpha1-/- mice.
• IL-11Ralpha1-/- mice responded to ovariectomy and estradiol treatment similarly to wildtype mice.

Conclusions:

• IL-11 signaling is critical for regulating normal bone turnover and maintaining trabecular bone mass.
• The absence of IL-11Ralpha leads to increased bone mass primarily due to reduced osteoclast differentiation, independent of IL-6 signaling.
• IL-11 signaling is not required for the skeletal responses to estrogen deficiency or estradiol administration.