Osteoimmunology and Its Implications for Transplantation

Pacifici, Roberto

doi:10.1111/ajt.12380

Cited by 40 publications

(41 citation statements)

References 87 publications

(118 reference statements)

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“…It has been reported that activated Th17 produces high levels of IL‐17, IL‐23, RANKL, TNF, and low levels of IFN‐γ. Consequently, IL‐17 promotes the production of RANKL, IL‐1β, and TNF and plays a role in bone resorption . The role of Th1 and Th2 cells in bone remodeling is to regulate inflammation via their signature cytokine IFN‐γ and IL‐4 respectively.…”

Section: Triggers and Targetsmentioning

confidence: 99%

The underlying pathophysiology and therapeutic approaches for osteoporosis

Awasthi

Mani

Singh

et al. 2018

Medicinal Research Reviews

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With an increase in the ageing population worldwide, the prevalence of osteoporosis increases at an alarming rate in both male and female irrespective of their ethnicity. At present, the currently available therapeutic options are mostly limited to either bone resorptive or bone forming efficacies and both approaches are associated with serious side effects. Despite these options, there is still need for newer therapeutics to treat osteoporosis, which can offer beneficial effects for maintaining balanced dynamics between bone formation and bone resorption, devoid of any side effect. The proper understanding of pathophysiology of the disease is essential for designing or investigating an effective and safe anti-osteoporotic agent. This review represents a discussion around the molecular targets with their implications in disease progression, available therapeutic options, the emerging targets, and the importance of designing an effective anti-osteoporotic agent.

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Section: Triggers and Targetsmentioning

confidence: 99%

The underlying pathophysiology and therapeutic approaches for osteoporosis

Awasthi

Mani

Singh

et al. 2018

Medicinal Research Reviews

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“…The bone homeostasis is tightly regulated by osteoclast-mediated bone resorption and associated osteoblast/osteocyte-mediated bone formation (1–3). Recent studies from the osteoimmunology field highlight the critical role of the immune system in the regulation of bone homeostasis in both physiological and pathological conditions (4–8). Chronic inflammation such as occurs in rheumatoid arthritis and periodontitis is one of the most common pathological conditions associated with excessive bone loss.…”

Section: Introductionmentioning

confidence: 99%

Def6 Restrains Osteoclastogenesis and Inflammatory Bone Resorption

Binder

Miller

Yoshida

et al. 2017

The Journal of Immunology

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Inflammatory bone resorption mediated by osteoclasts is a major cause of morbidity and disability in many inflammatory disorders, including rheumatoid arthritis (RA). The mechanisms that regulate osteoclastogenesis and bone resorption in inflammatory settings are complex and have not been well elucidated. In this study, we identify the immunoregulator Def6 as a novel inhibitor of osteoclastogenesis in both physiological and inflammatory conditions. Def6 deficiency in Def6−/− mice enhanced the sensitivity of osteoclast precursors to the physiological osteoclastogenic inducer RANKL, and Def6−/− osteoclasts formed actin rings. Furthermore, Def6 deficiency markedly increased TNF-α-induced osteoclastogenesis both in vitro and in vivo and enhanced bone resorption in an inflammatory osteolysis mouse model. TNF-α serum levels negatively correlated with Def6 expression levels in osteoclast precursors obtained from RA patients and the osteoclastogenic capacity of the osteoclast precursors was significantly inversely correlated with their Def6 expression levels, indicating that Def6 functions as an inhibitor of excessive osteoclast formation and bone destruction in RA. Mechanistically, Def6 suppressed osteoclastogenesis and the expression of key osteoclastogenic factors NFATc1, Blimp1 and c-Fos by regulating an endogenous IFN-β mediated autocrine feedback loop. The Def6-dependent pathway may represent a novel therapeutic target to prevent pathological bone destruction.

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“…Translational studies have reported that lymphoid cells express parathyroid hormone (PTH) receptors and mice lacking T cells cannot induce osteoclast formation in response to PTH infusion and are resistant to cortical bone resorption. 10 Following allo-SCT the immune system is upregulated. Thus, cortical bone loss may result from an amplified interaction of lymphocytes with circulating PTH.…”

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confidence: 99%