Abstract
The study of the immunoskeletal interface has led to the discovery of numerous cytokines involved in the regulation of bone remodeling, providing valuable information on the pathogenesis of osteoporosis. The role of inflammatory cytokines of the Th1 and Th17 profile in osteoporosis is well known. Here we focus on two newly discovered Th2 cytokines, IL-31 and IL-33, whose implications in osteoporosis are recently emerging. Clinical and experimental observations suggest an important role of the IL-33/IL-31 axis in osteoporosis. IL-33 induces IL-31 secretion by Th2 cells and inhibits RANKL-dependent osteoclastogenesis, thus counteracting bone loss. IL-31 influences Th1/Th17 osteoclastogenetic inflammation and limits Th2 osteoprotective processes, thus favoring osteoporosis. Better knowledge of the role of IL-31 and IL-33 and their receptor complexes in osteoporosis could provide an interesting perspective for the development of new and more effective therapies, possibly with less side effects.
Highlights
Osteoporosis is a predominantly female pathology of the skeleton characterized by loss of bone mass, decreased bone mineral density (BMD), and derangement of bone microarchitecture, which lead to a compromised physical strength of the bone and increased fragility of the skeleton, exposing patients to a greater risk of fractures on minor trauma [1]
There is evidence that receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL) derived from osteocytes is responsible for the bone loss associated with unloading, whereas RANKL produced by osteoblasts or their progenitors does not contribute to adult bone remodeling
The final effects of the IL-33/IL-31 axis on bone is heavily determined by the complexity underlying their reciprocal influences
Summary
Osteoporosis is a predominantly female pathology of the skeleton characterized by loss of bone mass, decreased bone mineral density (BMD), and derangement of bone microarchitecture, which lead to a compromised physical strength of the bone and increased fragility of the skeleton, exposing patients to a greater risk of fractures on minor trauma [1]. Each cytokine of the complex network of regulatory factors involved in bone remodeling has pleiotropic functions and exerts different effects depending on the target cells and the influence of other cytokines in the specific microenvironment [23,24] Osteoclastogenic cytokines, such as interleukin (IL)-6, IL-17, interferon (IFN)-γ and tumor necrosis factor (TNF)-α, the macrophage-colony stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1), promote bone resorption and inhibit osteoblasts, whereas other cytokines, such as IL-4, IL-10, transforming growth factor (TGF)-β, and IL-12, suppress osteoclasts and promote osteogenesis. M1 macrophages, through immunomodulatory factors (cytokines and chemokines) secretion, stimulate pro-inflammatory cytokine expression and bone loss, whereas M2 macrophages, through vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2 secretion, exert anti-inflammatory functions promoting bone repair Taken together, these findings suggest that osteoporosis is determined by a complex overlap of different factors. The role of the IL-33/ST2 axis in Th2/IL-31 and Th17 immune responses, characterizing the development of allergic respiratory diseases, has been recently clarified [38,39], the relationship between IL-31 and IL-33 in osteoporosis is quite peculiar and the data from the literature are often contradictory
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
