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

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 ligandspecific-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.

Platelet-Rich Fibrin Increases CXCL8 Expression in Gingival Fibroblasts

“…In this context, we have identified PRF as causing a robust increase in IL11 [ 15 ] expression in gingival fibroblasts, an effect that can be traced back to the activation of TGF-β signaling provoked by PRF. IL11, in turn, is a potent pleiotropic cytokine that drives the gp130—IL6-family signaling pathway in various cell types with a prominent role in tissue homeostasis, including bone [ 30 ], also causing pathological changes related to fibrosis [ 31 ]. Our present goal is to identify further genes targeted by PRF that may be linked to the autocrine and paracrine activity of gingival fibroblasts, which is, in the present study, CXCL8.…”