Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis

Walsh, Nicole C.; Reinwald, Susan; Manning, Catherine A.; Condon, Keith W.; Iwata, Ken; Karmakar, Sougata; Burr, David B.; Gravallese, Ellen M.

doi:10.1016/j.bone.2009.01.349

Cited by 63 publications

(101 citation statements)

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“…In addition to increased osteoclastogenesis, bone formation is also compromised in arthritis at sites of focal bone erosion (4,41). MSCs derived from mouse bone tend to lose their differentiation potential in the presence of proinflammatory cytokines (42).…”

Section: Discussionmentioning

confidence: 99%

Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis

Garimella

Kour

Piprode

et al. 2015

The Journal of Immunology

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)–induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance.

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Section: Discussionmentioning

confidence: 99%

Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis

Garimella

Kour

Piprode

et al. 2015

The Journal of Immunology

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“…The cytokine milieu created by cells present within the inflammatory infiltrate in RA promotes increased expression of RANKL relative to OPG resulting in increased osteoclast differentiation and promotion of bone resorption at sites where the inflammatory tissue is adjacent to bone (66)(67)(68). In addition to increased osteoclastic bone resorption, differentiation of osteoblasts is compromised at bone surfaces adjacent to erosion (69), thereby contributing to net bone loss at this site. Increased levels of IL-6, OSM, IL-11, LIF, IL-27 and the soluble form of IL-6R (sIL-6R) have been detected in RA synovial fluids and/or tissues (70)(71)(72)(73) (Table 1).…”

Section: Gp130 Cytokines In Rheumatoid Arthritismentioning

confidence: 99%

GP130 cytokines and bone remodelling in health and disease

Sims¹,

Walsh²

2010

BMB Reports

105

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Gp130 cytokinesGlycoprotein 130 (gp130) is a receptor subunit capable of intracellular signalling that is required for the cellular action of a wide range of cytokines. The most well known of these are interleukin (IL-) 6 and IL-11, leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF). Every cytokine that binds to gp130 generates specific intracellular signalling events by forming specific receptor:ligand complexes, each with distinct components and/or architecture (Fig.

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“…Bone surfaces adjacent to inflammation have decreased bone formation rates, associated with lower expression of markers of mature OBs [65,66]. Given the inhibitory effects of TNFα on OB differentiation discussed above, it is likely that classical NF-κB activation is involved in the decreased bone formation.…”

Section: Tnfr1mentioning

confidence: 99%

Role of NF-κB in the skeleton

2010

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Since the discovery that deletion of the NF-κB subunits p50 and p52 causes osteopetrosis in mice, there has been considerable interest in the role of NF-κB signaling in bone. NF-κB controls the differentiation or activity of the major skeletal cell types -osteoclasts, osteoblasts, osteocytes and chondrocytes. However, with five NF-κB subunits and two distinct activation pathways, not all NF-κB signals lead to the same physiologic responses. In this review, we will describe the roles of various NF-κB proteins in basal bone homeostasis and disease states, and explore how NF-κB inhibition might be utilized therapeutically.

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Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis

Cited by 63 publications

References 0 publications

Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis

Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis

GP130 cytokines and bone remodelling in health and disease

Role of NF-κB in the skeleton

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