Osteoimmunology: A Current Update of the Interplay Between Bone and the Immune System

Abstract

Immunology, already a discipline in its own right, has become a major part of many different medical fields. However, its relationship to orthopedics and trauma surgery has unfortunately, and perhaps unjustly, been developing rather slowly. Discoveries in recent years have emphasized the immense breadth of communication and connection between both systems and, importantly, the highly promising therapeutic opportunities. Recent discoveries of factors originally assigned to the immune system have now also been shown to have a significant impact on bone health and disease, which has greatly changed how we approach treatment of bone pathologies. In case of bone fracture, immune cells, especially macrophages, are present throughout the whole healing process, assure defense against pathogens and discharge a complex variety of effectors to regulate bone modeling. In rheumatoid arthritis and osteoporosis, the immune system contributes to the formation of the pathological and chronic conditions. Fascinatingly, prosthesis failure is not at all solely a mechanical problem of improper strain but works in conjunction with an active contribution of the immune system as a reaction to irritant debris from material wear. Unraveling conjoined mechanisms of the immune and osseous systems heralds therapeutic possibilities for ailments of both. Contemplation of the bone as merely an unchanging support pillar is outdated and obsolete. Instead it is mandatory that this highly diverse network be incorporated in our understanding of the immune system and hematopoiesis.

Ganoderma lucidum Immune Modulator Protein rLZ-8 Could Prevent and Reverse Bone Loss in Glucocorticoids-Induced Osteoporosis Rat Model

“…Besides the small molecules mentioned above, LZ-8, first FIP family protein isolated from G. lucidum (Kino et al, 1989), functioned as immune modulator in immune cell and cancer cell (Haak-Frendscho et al, 1993;Huang et al, 2009). Accumulating evidences in osteoimmunology field suggested that immune modulation was a promising anti-osteoporosis strategy (Tsukasaki and Takayanagi, 2019;Guder et al, 2020). Therefore, we hypothesized that LZ-8 might affect osteoporosis through immune modulation.…”

CD4+ T Cell Profile and Activation Response in Sickle Cell Disease Patients with Osteonecrosis

“…Previous studies have shown that activated T cells play an important role in bone health and disease. Especially, Th17 cells have a great influence on bone metabolism by secreting characteristic soluble factor that induces osteoclastogenesis [ 35 ]. In contrast, effector T cell production of IFN- γ strongly suppresses bone resorption by interfering with the RANKL/RANK signaling pathway [ 36 ].…”

Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons

“…Different signaling pathways of these and other cells of the immune system regulate their function and bone remodeling (25)(26)(27)(28)(29) (Figure 2). Indeed, the bone and the immune system maintain a close relationship both anatomicalsince the bone houses the bone marrow-and functional through different molecular and cellular signaling pathways and a myriad of cytokines (25,26,28,29). Accordingly, osteoimmunology is a discipline that attempts to address all these interrelations (30) and has undergone a great development in recent years.…”

“…They are proteins belonging to the TNF superfamily. RANKL is expressed, both soluble and membrane-bound forms, in different bone cells (osteoblasts and osteoclasts) and also in different cell subsets of the immune system (25,28,29). By contrast, RANK is mainly expressed in osteoclasts.…”