The cytokine interleukin-11 crucially links bone formation, remodeling and resorption.

Bone development is a complex process that requires the activity of several different signaling pathways and cell types. It involves the coordinated action of osteoclasts (cells that are capable of resorbing bone), osteoblasts (cells that are able to form bone), osteocytes (cells that form a syncytial network within the bone), skeletal muscle cells and the bone marrow. In recent years, the cytokine interleukin-11 (IL-11), a member of the IL-6 family of cytokines, has emerged as an important regulatory protein for bone formation, remodeling and resorption. Furthermore, coding missense mutations in the IL11RA gene, which encodes the IL-11 receptor (IL-11R), have recently been linked to craniosynostosis, a human disease in which the sutures that line the head bones close prematurely. This review summarizes current knowledge about IL-11 and highlights its role in bone development and homeostasis. It further discusses the specificity and redundancy provided by the other members of the IL-6 cytokine family and how they facilitate signaling and cross-talk between skeletal muscle cells, bone cells and the bone marrow. We describe their actions in physiological and in pathological states and discuss how this knowledge could be translated into therapy.