The Emerging Role of Interleukin-(IL)-11/IL-11R in Bone Metabolism and Homeostasis: From Cytokine to Osteokine

Aging Dis. 2023 Dec 1;14(6):2113-2126. doi: 10.14336/AD.2023.0306.

Abstract

Interleukin-(IL)-11 is a cytokine involved in hematopoiesis, cancer metastasis, and inflammation. IL-11 belongs to the IL-6 cytokine family, binding to the complex of receptors glycoprotein gp130 and the ligand-specific-receptor subunits (IL-11Rα or their soluble counterpart sIL-11R). IL-11/IL-11R signaling enhances osteoblast differentiation and bone formation and mitigates osteoclast-induced bone resorption and cancer bone metastasis. Recent studies have shown that systemic and osteoblast/osteocyte-specific IL-11 deficiency leads to reduced bone mass and formation, but also adiposity, glucose intolerance, and insulin resistance. In humans, mutations of IL-11 and the receptor IL-11RA genes are associated with height reduction, osteoarthritis, and craniosynostosis. In this review, we describe the emerging role of IL-11/IL-11R signaling in bone metabolism by targeting osteoblasts, osteoclasts, osteocytes, and bone mineralization. Furthermore, IL-11 promotes osteogenesis and suppresses adipogenesis, thereby influencing the fate of osteoblast/adipocyte differentiation derived from pluripotent mesenchymal stem cells. We have newly identified IL-11 as a bone-derived cytokine that regulates bone metabolism and the link between bone and other organs. Thus, IL-11 is vital in bone homeostasis and could be considered a potential therapeutic strategy.

Publication types

  • Review

Grants and funding

This work is supported by National Natural Science Foundation of China (Grant No. 81600691), China Postdoctoral Science Foundation funded project (Grant No.2018M640615). Dr. Bingzi Dong thanks Prof. Toshio Matsumoto (Fujii Memorial Institute of Medical Science, Tokushima University, Japan) for long-term guidance and helpful advice. We thank Prof. Toshio Matsumoto for the perspective regarding the emerging role of IL-11 in bone metabolism.