Osteoimmunology — Bidirectional dialogue and inevitable union of the fields of bone and immunity —

Takayanagi, Hiroshi

doi:10.2183/pjab.96.013

Cited by 12 publications

(14 citation statements)

References 51 publications

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“…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.…”

Section: Bone Homeostasis and Bone Remodeling And The Immune Systemmentioning

confidence: 99%

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Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons

et al. 2020

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Osteoporosis has been classically considered a comorbidity of rheumatoid arthritis (RA). However, recent advances in the pathogenesis of osteoporosis in RA have shown a close interplay between cells of the immune system and those involved in bone remodeling, introducing new actors into the classic route in which osteoclast activation is related to the RANK/RANKL/OPG pathway. In fact, the inflammatory state in early stages of RA, mediated by interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α has the ability to activate and differentiate osteoclasts not only through their relationship with RANKL, but also through the Wnt/DKK1/sclerostin pathway, leading to bone loss. The role of synovial fibroblasts and activated T lymphocytes in the expression of the RANKL system and its connection to bone destruction is also depicted. In addition, autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are other pathogenic mechanisms for the development of bone erosions and systemic osteoporosis in RA, even before the onset of arthritis. The aim of this review is to unravel the relationship between different factors involved in the development of osteoporosis in RA patients, both the classic factors and the most novel, based on the relationship of autoantibodies with bone remodeling. Furthermore, we propose that bone mineral density measured by different techniques may be helpful as a biomarker of severity in early arthritis patients.

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Section: Bone Homeostasis and Bone Remodeling And The Immune Systemmentioning

confidence: 99%

“…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.…”

Section: Increased Bone Resorption In Ramentioning

confidence: 99%

Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons

et al. 2020

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“…Initiating the targeting of osteoclasts in the treatment of rheumatoid arthritis is one of the important fruits of osteoimmunology. (29) We performed a meta-analysis of ve randomized-controlled trials evaluating the e cacy and safety of denosumab in the treatment of rheumatoid arthritis. These results provide strong evidence to suggest that denosumab can prevent the progression of bone erosion in RA patients.…”

Section: Discussionmentioning

confidence: 99%

Denosumab in the treatment on structural damage caused by rheumatoid arthritis: a systematic review and meta-analysis

Cai

Zhang

Cheng

et al. 2021

Preprint

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Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. The effects of denosumab in patients with RA have been analyzed in several clinical studies. These results provide strong evidence to suggest that denosumab significantly inhibited the progression of bone erosion, increased BMD in patients with RA. We undertook a meta-analysis to summarize the efficacy and safety of denosumab in the treatment on structural damage caused by rheumatoid arthritis.Methods: We searched PubMed, Embase, Medline, The Cochrane Library, and collected randomized controlled trials of denosumab in patients with rheumatoid arthritis from the database was established until January 19, 2021.Literature was screened according to inclusion and exclusion criteria, and RevMan 5.3 software was used for Meta-analysis after quality assessment.Results: Five eligible studies were included in the primary meta-analysis. Denosumab significantly inhibited the increase of the modified Sharp erosion score(MD=-0.62, 95%CI＝-0.91～-0.33,P＜0.0001)、modified total Sharp score(MD=-0.78, 95%CI＝1.23～-0.33,P=0.0007)compared to placebo groups at 12 months. In addition, denosumab also significantly increased lumbar spine BMD (3.73, 95% CI 2.00, 5.46, P<0.0001) compared to placebo or bisphosphonates. There was no evidence of an effect of denosumab on joint space narrowing. Adverse events, serious adverse events were similar between denosumab and placebo arms.Conclusion: Results suggest that denosumab inhibits the progression of structural damage caused by rheumatoid arthritis, with no increase in the rates of adverse events as compared with control group. Preliminary research suggests that denosumab is reasonable and promising options for preventing and treating structural destruction in rheumatoid arthritis.Trial registration: We registered our study with PROSPERO (registration number CRD42021239783); no other meta-analysis focusing on denosumab use for structural damage caused by rheumatoid arthritis were found in the PROSPERO database.

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“…Finally, during bone remodeling, monocytes can also produce osteoclasts that act in concert with osteoblasts to maintain an equilibrium bone mass. While osteoclast progenitors express receptor activator of nuclear factor kappa-Β (RANK), which binds to osteoblast-associated receptor activator of nuclear factor kappa-Β ligand (RANKL) and signals for osteoclast differentiation and bone resorption, hMSCs are able to produce a soluble decoy receptor called osteoprotegerin (OPG) that binds RANKL and inhibits RANK signaling to reduce osteoclast activity [14-17]. An increase in secreted OPG has been linked to less resorption by osteoclasts on mineralized collagen scaffolds and provides a route to improve early stage graft integration with the surrounding wound site and improved quantity and quality of bone repair [14, 15].…”

Section: Introductionmentioning

confidence: 99%

Glycosaminoglycan content of a mineralized collagen scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation

Dewey

Kolliopoulos

Ngo

et al. 2021

Preprint

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Effective design of biomaterials to aid regenerative repair of craniomaxillofacial (CMF) bone defects requires approaches that modulate the complex interplay between exogenously added progenitor cells and cells in the wound microenvironment, such as osteoblasts, osteoclasts, endothelial cells, and immune cells. We are exploring the role of the glycosaminoglycan (GAG) content in a class of mineralized collagen scaffolds recently shown to promote osteogenesis and healing of craniofacial bone defects. We previously showed that incorporating chondroitin-6-sulfate or heparin improved mineral deposition by seeded human mesenchymal stem cells (hMSCs). However, improved healing requires angiogenic processes as well as an immune response. Here, we examine the effect of varying scaffold GAG content on hMSC behavior, specifically with regards to their ability to act as endogenous factories of biomolecules that modulate processes associated with osteoclastogenesis, vasculogenesis, and the immune response. We report the role of hMSC-conditioned media produced in mineralized scaffolds containing chondroitin-6-sulfate (CS6), chondroitin-4-sulfate (CS4), or heparin (Heparin) GAGs on biomarkers of endothelial tube formation and monocyte differentiation towards macrophage and osteoclast lineages. Notably, endogenous production by hMSCs within Heparin scaffolds most significantly inhibits osteoclastogenesis via secreted osteoprotegerin (OPG), while the secretome generated by CS6 scaffolds reduced pro-inflammatory immune response and increased endothelial tube formation. Modulation of endogenous factor production by seeded hMSCs via scaffold GAG content is sufficient to down-regulate many pro- and anti-inflammatory cytokines, such as IL6, IL-1β, and CCL18 and CCL17 respectively. Together, these findings demonstrate that modifying mineralized collagen scaffold GAG content can both directly (hMSC activity) and indirectly (endogenous production of secreted factors) influence overall osteogenic potential and mineral biosynthesis as well as angiogenic potential and monocyte differentiation towards osteoclastic and macrophage lineages. Scaffold GAG content is therefore a powerful stimulus to modulate reciprocal signaling between multiple cell populations within the bone healing microenvironment.

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Osteoimmunology — Bidirectional dialogue and inevitable union of the fields of bone and immunity —

Cited by 12 publications

References 51 publications

Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons

Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons

Denosumab in the treatment on structural damage caused by rheumatoid arthritis: a systematic review and meta-analysis

Glycosaminoglycan content of a mineralized collagen scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation

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