Osteoimmunology: memorandum for rheumatologists

Abstract

Rapid progress has been made in exploring the connections between the skeletal system and the immune system over the past decade. Bone tissue forms developmental niches for hematopoietic stem cells, and activated immune cells are involved in bone metabolism regulation and are potent mediators of osteoporosis and bone erosion under pathological conditions. The interdisciplinary field of osteoimmunology has emerged to pool the knowledge of the interdependence of these two systems, including the shared ligands and receptors, their crosstalk and interaction, and common intracellular signaling pathways with bidirectional influence. The receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) triad is the key vinculum, with multifaceted potency, being not only essential for osteoclastogenesis but also critical for lymph node organogenesis and lymphopoiesis as well as for immune regulation. In this review, we summarize the progress in this area, focusing on those aspects of interest concerning rheumatic diseases. osteoimmunology, bone remodeling, osteoclastogenesis, immune cells, RANKLCitation:

Protective Effects of Punicalagin on Osteoporosis by Inhibiting Osteoclastogenesis and Inflammation via the NF-κB and MAPK Pathways

“…Recent findings led to a research focus on different proinflammatory factors, as well as their role in osteoclastogenesis (Pietschmann et al, 2016;Michalski and McCauley, 2017). Estrogen withdrawal will lead to an increase in inflammatory cytokines, and these mediators majorly contribute to excessive osteoclastogenesis and bone resorption in menopause-associated bone loss (Zhao et al, 2016;Pietschmann et al, 2016;Michalski and McCauley, 2017). As PUN has considerable anti-inflammatory effects (Wang et al, 2019), we wondered whether PUN can suppress inflammation in osteoporosis.…”

“…We confirmed that PUN directly inhibited osteoclastogenesis in vitro. Growing evidence indicates that inflammation plays an important role during osteoclast formation and bone resorption (Zhao et al, 2016). Therefore, we next examined whether PUN has a direct inhibitory effect on inflammation.…”

“…Excessive osteoclastogenesis and bone resorption result in changes in trabecular bone mass and microstructure, leading to the potential risk of fracture; this indicates the need to find therapeutic approaches to prevent osteoporosis (Eriksen et al, 2014;Chen et al, 2019;Jacome-Galarza et al, 2019). Osteoporosis is also considered a chronic inflammatory disease, as several increased proinflammatory cytokines, including tumor necrosis factor (TNF-a), interleukin (IL)-1b, and IL-6, may regulate RANKL expression (Zhao et al, 2016;Michalski and McCauley, 2017;Zeng et al, 2019). Therefore, inhibiting proinflammatory osteoclastogenesis activation could be a promising strategy for the discovery of antiosteoporosis drugs.…”

Prevention and Treatment of Osteoporosis Using Chinese Medicinal Plants: Special Emphasis on Mechanisms of Immune Modulation

“…However, osteoimmunology demonstrated that the immune system and immune factors may be involved in the development of osteoporosis and play important regulatory roles [ 2 , 3 ]. The microenvironment created by bone cells provides conditions for development of the immune system, which regulates bone metabolism via B cells, T cells, dendritic cells, and many cytokines [ 2 – 5 ]. Abnormal activation of the immune system alters the balance between osteoblasts and osteoclasts, which results in an imbalance in bone remodeling and causes osteoporosis [ 6 – 8 ].…”

Regional immunity in tissue homeostasis and diseases

“…The development and response of immune cells associate to bone remodeling; on the other hand, activated immune cells are involved in bone metabolism regulation, and mediate osteoporosis and bone erosion under pathological conditions such as rheumatoid arthritis (RA), spondyloarthropathy (SPA), osteoporosis (OP), and periodontal disease (PD). In this issue, Zhao et al presented current understanding of osteoimmunology and emphasized on the RANK/RANKL/OPG signaling in bone remodeling and immune responses (Zhao et al, 2016). Recent research progress in the interactions between T cells, B cells, DCs and bone cells, in the role of several kinds of cytokines including M-CSF, TNF-α, IL-1, IFN-γ, IL-4, IL-10, IL-6, TGF-β, OPN and complement system in bone homeostasis were also summarized in this review, particularly their pathogenesis in major diseases.…”