The increased in vitro osteoclastogenesis in patients with rheumatoid arthritis is due to increased percentage of precursors and decreased apoptosis — The In Vitro Osteoclast Differentiation in Arthritis (IODA) study

Durand, Marianne; Boire, Gilles; Komarova, Svetlana V.; Dixon, S. Jeffrey; Sims, Stephen M.; Harrison, Rene E.; Nabavi, Noushin; Maria, Osama Muhammad; Manolson, Morris F.; Mizianty, Marcin J.; Kurgan, Lukasz; Brum‐Fernandes, Artur J. de

doi:10.1016/j.bone.2010.10.167

Cited by 41 publications

(37 citation statements)

References 30 publications

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“…Based on the present results, we conclude that osteoclastogenesis may be promoted in Bach1 high HO‐1 low macrophages from RA patients. Indeed, monocytes from RA patients tend to develop into OCs more readily than those from healthy controls (47). The findings suggest that HO‐1 is relatively deficient in local lesions and that HO‐1 supplementation could be a reasonable therapeutic approach in RA.…”

Section: Discussionmentioning

confidence: 99%

Bach1 regulates osteoclastogenesis in a mouse model via both heme oxygenase 1–dependent and heme oxygenase 1–independent pathways

Kirino¹,

Takeno²,

Takase³

et al. 2012

Arthritis & Rheumatism

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Objective. Reducing inflammation and osteoclastogenesis by heme oxygenase 1 (HO-1) induction could be beneficial in the treatment of rheumatoid arthritis (RA). However, the function of HO-1 in bone metabolism remains unclear. This study was undertaken to clarify the effects of HO-1 and its repressor Bach1 in osteoclastogenesis.Methods. In vitro osteoclastogenesis was compared in Bach1-deficient and wild-type mice. Osteoclasts (OCs) were generated from bone marrow-derived macrophages by stimulation with macrophage colonystimulating factor and RANKL. Osteoclastogenesis was assessed by tartrate-resistant acid phosphatase staining and expression of OC-related genes. Intracellular signal pathways in OC precursors were also assessed. HO-1 short hairpin RNA (shRNA) was transduced into Bach1؊/؊ mouse bone marrow-derived macrophages to examine the role of HO-1 in osteoclastogenesis. In vivo inflammatory bone loss was evaluated by local injection of tumor necrosis factor ␣ (TNF␣) into calvaria. Results. Transcription of HO-1 was downregulated by stimulation with RANKL in the early stage of OC differentiation. Bach1؊/؊ mouse bone marrowderived macrophages were partially resistant to the RANKL-dependent HO-1 reduction and showed impaired osteoclastogenesis, which was associated with reduced expression of RANK and components of the downstream TNF receptor-associated factor 6/c-Fos/ NF-ATc1 pathway as well as reduced expression of Blimp1. Treatment with HO-1 shRNA increased the number of OCs and expression of OC-related genes except for the Blimp1 gene during in vitro osteoclastogenesis from Bach1 ؊/؊ mouse bone marrow-derived macrophages. TNF␣-induced bone destruction was reduced in Bach1 ؊/؊ mice in vivo. Conclusion. The present findings demonstrate that Bach1 regulates osteoclastogenesis under inflammatory conditions, via both HO-1-dependent and HO-1-independent mechanisms. Bach1 may be worthy of consideration as a target for treatment of inflammatory bone loss in diseases including RA.

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Section: Discussionmentioning

confidence: 99%

Bach1 regulates osteoclastogenesis in a mouse model via both heme oxygenase 1–dependent and heme oxygenase 1–independent pathways

Kirino¹,

Takeno²,

Takase³

et al. 2012

Arthritis & Rheumatism

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“…We have recently shown that the capacity to generate osteoclasts in vitro from precursors in the peripheral blood varies markedly in a population of healthy controls, and that the phenotype of being a high or low differentiator is stable over time (10). This finding led to the In vitro Osteoclast Differentiation in Arthritis (IODA) study, the objective of which is to investigate the relationships between osteoclastogenic capacity and inflammatory and degenerative joint diseases.…”

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confidence: 99%

Monocytes from patients with osteoarthritis display increased osteoclastogenesis and bone resorption: The In Vitro Osteoclast Differentiation in Arthritis study

Durand

Komarova

Bhargava

et al. 2012

Arthritis & Rheumatism

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Objective. To compare the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) from patients with osteoarthritis (OA) to that of PBMCs from self-reported normal individuals. Methods.PBMCs from 140 patients with OA and 45 healthy donors were assayed for CD14؉ expression and induced to differentiate into osteoclasts over 3 weeks in vitro. We assessed the number of osteoclasts, their resorptive activity, osteoclast apoptosis, and expression of the following cytokine receptors: RANK, interleukin-1 receptor type I (IL-1RI), and IL-1RII. A ridge logistic regression classifier was developed to discriminate OA patients from controls.Results. PBMCs from OA patients gave rise to more osteoclasts that resorbed more bone surface than did PBMCs from controls. The number of CD14؉ precursors was comparable in both groups, but there was less apoptosis in osteoclasts obtained from OA patients. Although no correlation was found between osteoclastogenic capacity and clinical or radiographic scores, levels of IL-1RI were significantly lower in cultures from patients with OA than in cultures from controls. Osteoclast apoptosis and expression levels of IL-1RI and IL-1RII were used to build a multivariate predictive model for OA.Conclusion. During 3 weeks of culture under identical conditions, monocytes from patients with OA display enhanced capacity to generate osteoclasts compared to cells from controls. Enhanced osteoclastogenesis is accompanied by increased resorptive activity, reduced osteoclast apoptosis, and diminished IL-1RI expression. These findings support the possibility that generalized changes in bone metabolism affecting osteoclasts participate in the pathophysiology of OA. (83330) Drs. Komarova, Manolson, Harrison, Dixon, Sims, Kurgan, Boire, and de Brum-Fernandes are named inventors on a patent application for a diagnostic method and prognostic tool for osteoarthritis and the uses thereof. Dr. Boire has received consulting fees, speaking fees, and/or honoraria from Warner Chilcott, Merck, Pfizer, Supported by a New Emerging Team Grant

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“…Osteoclast differentiation and resorption activity is increased following the increase of monocyte progenitors in RA patients. Osteoclast apoptosis in vitro is also decreased [30,31]. It is also reported that synovial membrane infiltrated macrophages express TRAP and calcitonin receptor.…”

Section: Main Subjects Osteoclasts Differentiation and Activation In mentioning

confidence: 79%

Osteoclasts: Crucial in Rheumatoid Arthritis

Jeong

Kim

2016

J Rheum Dis

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Osteoclasts are a major component of bone metabolism in physiologic condition and in rheumatoid arthritis (RA). RA is a chronic, autoimmune, inflammatory disease primarily affecting the joints. Joint inflammation leads to cartilage and bone destruction by osteoclast activation. This osteoclast activation leads to typical RA symptoms and is the therapeutic target. Several kinds of drugs are used for preventing bone loss by osteoclasts in RA patients. However, the bone destructive action of osteoclasts is not the only mechanism in RA pathogenesis. Recent research suggests that the osteoclasts regulate hematopoietic stem cell niches and invoke immune responses in bone. Osteoclasts are derived from bone marrow hematopoietic stem cells, and maintain the hematopoietic stem cell niches contract with osteoblasts. Osteoclasts secret several cytokines to regulate inflammation and T cell differentiation, and present antigen to T cells via major histocompatibility complex class I and class II molecules. Osteoclast concepts in both origins and functions are under major reconsideration and research. In this review, we will discuss these new insights. (J Rheum Dis 2016;23:141-147)

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The increased in vitro osteoclastogenesis in patients with rheumatoid arthritis is due to increased percentage of precursors and decreased apoptosis — The In Vitro Osteoclast Differentiation in Arthritis (IODA) study

Cited by 41 publications

References 30 publications

Bach1 regulates osteoclastogenesis in a mouse model via both heme oxygenase 1–dependent and heme oxygenase 1–independent pathways

Bach1 regulates osteoclastogenesis in a mouse model via both heme oxygenase 1–dependent and heme oxygenase 1–independent pathways

Monocytes from patients with osteoarthritis display increased osteoclastogenesis and bone resorption: The In Vitro Osteoclast Differentiation in Arthritis study

Osteoclasts: Crucial in Rheumatoid Arthritis

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