Roles of IL-11 in the regulation of bone metabolism

Abstract

Bone metabolism is the basis for maintaining the normal physiological state of bone, and imbalance of bone metabolism can lead to a series of metabolic bone diseases. As a member of the IL-6 family, IL-11 acts primarily through the classical signaling pathway IL-11/Receptors, IL-11 (IL-11R)/Glycoprotein 130 (gp130). The regulatory role of IL-11 in bone metabolism has been found earlier, but mainly focuses on the effects on osteogenesis and osteoclasis. In recent years, more studies have focused on IL-11's roles and related mechanisms in different bone metabolism activities. IL-11 regulates osteoblasts, osteoclasts, BM stromal cells, adipose tissue-derived mesenchymal stem cells, and chondrocytes. It's involved in bone homeostasis, including osteogenesis, osteolysis, bone marrow (BM) hematopoiesis, BM adipogenesis, and bone metastasis. This review exams IL-11's role in pathology and bone tissue, the cytokines and pathways that regulate IL-11 expression, and the feedback regulations of these pathways.

Keywords: IL-11; bone; immunity; metabolism; systematic review.

Figure 1

Roles of IL-11 in bone formation and bone resorption. IL-11 induces osteoblast differentiation and promotes the transcription of BSP through the MAPK, Wnt, and other signaling pathways. IL-11 can also induce osteoclast formation and different bone diseases.

Figure 2

Cytokines and pathways that regulate the expression of IL-11 in bone formation. Hormones, for example, TSH, PTH and glucocorticoids, can regulate the expression and secretion of IL-11. Cytokines and cell aging will also affect the secretion of IL-11.

Figure 3

Cytokines and pathways that regulate the expression of IL-11 in bone resorption. IL-1, tumor necrosis factor (TNF)-α, PTH, TSH, TGF-β, polyphosphate, and prostaglandin E2 (PGE2) can regulate IL-11’s osteolytic activity.