Increased bone resorption and osteopenia are a part of the lymphoproliferative phenotype of mice with systemic over-expression of interleukin-7 gene driven by MHC class II promoter

Salopek, Daniela; Grčević, Danka; Katavić, Vedran; Kovačić, Nataša; Lukić, Ivan; Marušić, Ana

doi:10.1016/j.imlet.2008.10.002

Cited by 25 publications

(15 citation statements)

References 24 publications

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“…Interestingly it was recently shown that mice overexpressing IL-7 were osteopenic. This effect was due to an increase in osteoclast numbers as well as activity, thus corroborating IL-7 as a factor potentiating osteoclast formation [41]. In another study, ovariectomy resulted in increased IL-7 levels, increased T-lymphocyte numbers and increased bone loss.…”

Section: Elevated Il-7 In B-cells Of Patients With Bone-lytic Diseasesmentioning

confidence: 63%

Osteoclast Formation from Peripheral Blood of Patients with Bone-lytic Diseases

Vries

Everts

2009

Clinic Rev Bone Miner Metab

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Recent literature indicates that osteoclast formation in vitro from peripheral blood of patients with diseases associated with bone loss such as rheumatoid arthritis, osteoporosis, periodontitis and bone metastatic cancer may occur spontaneously being independent of addition of osteoclast formation stimulating factors such as macrophage colony forming factor (M-CSF) and receptor activator of NFjB ligand (RANKL). This could provide important clues to our understanding on how osteoclast precursors are primed within the circulation whilst commuting to the site of ultimate osteoclast differentiation. When comparing the various bone-lytic diseases, the common view emerges that accessory cells, such as T-and B-lymphocytes provide osteoclastogenesis stimulating factors. The roles of B-and T-cells in providing osteoclastogenesis-positive signals such RANKL, TNF-a and IL-7 are discussed. Immune cells present in the circulation may play an important role in preparing the osteoclast precursor for its ultimate destiny, contributing to the bone resorbing multinucleated cell at the required bone site.

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Section: Elevated Il-7 In B-cells Of Patients With Bone-lytic Diseasesmentioning

confidence: 63%

Osteoclast Formation from Peripheral Blood of Patients with Bone-lytic Diseases

Vries

Everts

2009

Clinic Rev Bone Miner Metab

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“…To this end, we used the model of IL-7-induced bone loss in mice. This model has been shown to be associated with T cells and RANKL (16,17), thus mimicking inflammatory bone loss occurring in RA, which is also associated with increased IL-7 levels (11, 27, 28). However, the role of Th17 cells in this model is unclear.…”

Section: Il-7-induced Bone Loss In Vivo Is Associated With A2b1 Integmentioning

confidence: 97%

“…Groups of 10 mice were daily injected i.p. for 30 d with vehicle (PBS) or 10 mg/kg body weight recombinant human IL-7 to induce bone loss as previously described (15)(16)(17). The anti-a2b1 integrin blocking mAb (Ha1/29) and isotypic control mAb (Ha4/8) (50 mg/mouse) were injected i.p.…”

Section: Mice and Il-7-induced Bone Lossmentioning

confidence: 99%

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Cooperation between IL-7 Receptor and Integrin α2β1 (CD49b) Drives Th17-Mediated Bone Loss

Azreq

Arseneault

Boisvert

et al. 2015

The Journal of Immunology

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Th17 cells are critical effectors in inflammation and tissue damage such as bone erosion, but the mechanisms regulating their activation in this process are not fully understood. In this study, we considered the cooperation between cytokine receptors and integrin pathways in Th17-osteoclast function. We found that human Th17 cells coexpress IL-7R and the collagen-binding integrin α2β1 (CD49b), and IL-7 increases their adhesion to collagen via α2β1 integrin. In addition, coengagement of the two receptors in human Th17 cells cooperatively enhanced their IL-17 production and their osteoclastogenic function. The functional cooperation between IL-7R and α2β1 integrin involves activation of the JAK/PI3K/AKT (protein kinase B) and MAPK/ERK pathways. We also showed that IL-7–induced bone loss in vivo is associated with Th17 cell expansion. Moreover, blockade of α2β1 integrin with a neutralizing mAb inhibited IL-7–induced bone loss and osteoclast numbers by reducing Th17 cell numbers in the bone marrow and reducing the production of IL-17 and the receptor activator of NF-κB ligand. Thus, the cooperation between IL-7R and α2β1 integrin can represent an important pathogenic pathway in Th17-osteoclast function associated with inflammatory diseases.

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“…Osteopenia was the result of an increased number of active osteoclasts on the surface of trabecular bone. The overexpression of IL-7 also created an osteoclastogenic bone marrow microenvironment that promoted the commitment of precursors towards the osteoclast lineage [252]. …”

Section: Role Of the Immunoskeletal Interface In Estrogen Deficienmentioning

confidence: 99%

The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis

2013

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Although it has long been recognized that inflammation, a consequence of immune-driven processes, significantly impacts bone turnover, the degree of centralization of skeletal and immune functions has begun to be dissected only recently. It is now recognized that formation of osteoclasts, the bone resorbing cells of the body, is centered on the key osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL). Although numerous inflammatory cytokines are now recognized to promote osteoclast formation and skeletal degradation, with just a few exceptions, RANKL is now considered to be the final downstream effector cytokine that drives osteoclastogenesis and regulates osteoclastic bone resorption. The biological activity of RANKL is moderated by its physiological decoy receptor, osteoprotegerin (OPG). New discoveries concerning the sources and regulation of RANKL and OPG in physiological bone turnover as well as under pathological (osteoporotic) conditions continue to be made, opening a window to the complex regulatory processes that control skeletal integrity and the depth of integration of the skeleton within the immune response. This paper will examine the interconnection between bone turnover and the immune system and the implications thereof for physiological and pathological bone turnover.

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Increased bone resorption and osteopenia are a part of the lymphoproliferative phenotype of mice with systemic over-expression of interleukin-7 gene driven by MHC class II promoter

Cited by 25 publications

References 24 publications

Osteoclast Formation from Peripheral Blood of Patients with Bone-lytic Diseases

Osteoclast Formation from Peripheral Blood of Patients with Bone-lytic Diseases

Cooperation between IL-7 Receptor and Integrin α2β1 (CD49b) Drives Th17-Mediated Bone Loss

The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis

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