Macrophage colony-stimulating factor in patients with rheumatoid arthritis.

Kawaji, Hidemi; Yokomura, Koushi; Kikuchi, Kenichi; Somoto, Y; Shirai, Yoshio

doi:10.1272/jnms1923.62.260

Cited by 26 publications

(22 citation statements)

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“…Clinical scores for the mice were determined for each of the four paws on study days [16][17][18][19][20][21][22][23][24][25][26][27][28]. The scores for all the four paws were given using the following criteria: 0, normal joints; 1, swelling in one digit or joint or minimal diffuse erythema; 2, swelling in two digits or joints or mild diffuse erythema; 3, swelling in three digits or joints or moderate diffuse erythema; 4, swelling in four digits or joints or marked diffuse erythema; 5, severe diffuse erythema and severe swelling of the entire paw and rigid joints.…”

Section: Collagen-induced Arthritismentioning

confidence: 99%

“…SB1578 was administered orally twice daily to the mice only after the onset of disease (starting days [18][19][20][21][22], which was evident by swelling in at least one paw, and the treatment was continued for 10 d postenrollment. In the vehicle group, the clinical arthritic score rapidly increased from 0.52 6 0.2 on disease day 1 to 2.8 6 1.2 on disease day 11 (Fig.…”

Section: Amelioration Of Cia In Mice With Oral Administration Of Sb1578mentioning

confidence: 99%

“…Elevated levels of its ligand M-CSF are observed in the joints of RA patients, contributing to the development of macrophages and osteoclasts, which are the mediators of bone erosion (21)(22)(23)(24). Blockade of the M-CSF-c-Fms axis has been shown to inhibit the progression of arthritis in animal models indicating that it may play a pivotal role in the pathogenesis of RA (25,26).…”

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confidence: 99%

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SB1578, a Novel Inhibitor of JAK2, FLT3, and c-Fms for the Treatment of Rheumatoid Arthritis

Madan¹,

Goh²,

Hart³

et al. 2012

The Journal of Immunology

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SB1578 is a novel, orally bioavailable JAK2 inhibitor with specificity for JAK2 within the JAK family and also potent activity against FLT3 and c-Fms. These three tyrosine kinases play a pivotal role in activation of pathways that underlie the pathogenesis of rheumatoid arthritis. SB1578 blocks the activation of these kinases and their downstream signaling in pertinent cells, leading to inhibition of pathological cellular responses. The biochemical and cellular activities of SB1578 translate into its high efficacy in two rodent models of arthritis. SB1578 not only prevents the onset of arthritis but is also potent in treating established disease in collagen-induced arthritis mice with beneficial effects on histopathological parameters of bone resorption and cartilage damage. SB1578 abrogates the inflammatory response and prevents the infiltration of macrophages and neutrophils into affected joints. It also leads to inhibition of Ag-presenting dendritic cells and inhibits the autoimmune component of the disease. In summary, SB1578 has a unique kinase spectrum, and its pharmacological profile provides a strong rationale for the ongoing clinical development in autoimmune diseases.

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Section: Collagen-induced Arthritismentioning

confidence: 99%

Section: Amelioration Of Cia In Mice With Oral Administration Of Sb1578mentioning

confidence: 99%

mentioning

confidence: 99%

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SB1578, a Novel Inhibitor of JAK2, FLT3, and c-Fms for the Treatment of Rheumatoid Arthritis

Madan¹,

Goh²,

Hart³

et al. 2012

The Journal of Immunology

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“…CSF-1 promotes osteoclast development and bone degradation in vitro (11,12) and, thus, could contribute to the excessive osteoclast activity in osteoporosis and at sites of orthopedic implant failure (13,14). CSF-1 is elevated in the synovial fluid of rheumatoid arthritis patients (15), and synovial fibroblasts from rheumatoid arthritis patients produce high levels of CSF-1 (16), suggesting a role for CSF-1 in joint degradation. Increases in CSF-1 production are also associated with the accumulation of tissue macrophages seen in inflammatory bowel disease (17), glomerulonephritis (18), allograft rejection (19), and arteriosclerosis (20).…”

mentioning

confidence: 99%

Inhibition of colony-stimulating-factor-1 signalingin vivowith the orally bioavailable cFMS kinase inhibitor GW2580

Conway

McDonald

Parham

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

215

225

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Colony-stimulating-factor-1 (CSF-1) signaling through cFMS receptor kinase is increased in several diseases. To help investigate the role of cFMS kinase in disease, we identified GW2580, an orally bioavailable inhibitor of cFMS kinase. GW2580 completely inhibited human cFMS kinase in vitro at 0.06 M and was inactive against 26 other kinases. GW2580 at 1 M completely inhibited CSF-1-induced growth of mouse M-NFS-60 myeloid cells and human monocytes and completely inhibited bone degradation in cultures of human osteoclasts, rat calvaria, and rat fetal long bone. In contrast, GW2580 did not affect the growth of mouse NS0 lymphoblastoid cells, human endothelial cells, human fibroblasts, or five human tumor cell lines. GW2580 also did not affect lipopolysaccharide (LPS)-induced TNF, IL-6, and prostaglandin E2 production in freshly isolated human monocytes and mouse macrophages. After oral administration, GW2580 blocked the ability of exogenous CSF-1 to increase LPS-induced IL-6 production in mice, inhibited the growth of CSF-1-dependent M-NFS-60 tumor cells in the peritoneal cavity, and diminished the accumulation of macrophages in the peritoneal cavity after thioglycolate injection. Unexpectedly, GW2580 inhibited LPS-induced TNF production in mice, in contrast to effects on monocytes and macrophages in vitro. In conclusion, GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes.CSF-1 ͉ macrophage colony-stimulating factor

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“…Similarly, the enhanced osteoclastogenesis observed following deletion of the β3 integrin gene is due to stimulated M-CSF expression [25]. Regarding inflammatory osteolysis, the cytokine is increased in the serum of patients with RA [26] and those with severe ankylosing spondylitis [27], as well as in the synovial fluid around loose joint prostheses [28].…”

Section: The Role Of M-csf In Osteoclast Formation and Bone Remodelingmentioning

confidence: 99%

Effect of Macrophage Colony-Stimulating Factor Receptor c-Fms Antibody on Lipopolysaccharide-Induced Pathological Osteoclastogenesis and Bone Resorption

Kimura

Kitaura

Ishida

et al. 2015

Interface Oral Health Science 2014

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Lipopolysaccharide (LPS) is a major component of Gram-negative bacteria cell walls and is a well-known potent inducer of inflammation and pathogens of inflammatory bone loss. Formation of osteoclasts is highly dependent on the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Recent reports indicate that biological preparations, including anti-RANKL antibody and anti-tumor necrosis factor-α antibody, positively influence rheumatoid arthritis and osteoporosis. In this study, we aimed to investigate whether the M-CSF receptor c-Fms antibody would inhibit the formation of osteoclasts. C57BL6/J mice were injected with either LPS, LPS and anti-c-Fms antibody, anti-c-Fms antibody, or PBS into the supracalvariae. Animals were sacrificed and calvariae fixation and demineralization were performed. Histological sections of calvariae were stained for tartrate-resistant acid phosphatase (TRAP). In mice administered with both LPS and the anti-cFms antibody, osteoclast numbers were lower than those in mice administered with LPS alone. Moreover, levels of TRACP-5b, a bone resorption marker in mice serum, were lower in mice administered with both LPS and the anti-c-Fms antibody than in mice administered with LPS alone. These results suggest that M-CSF and its receptor are potential therapeutic targets in LPS-induced osteoclastogenesis, and that the anti-c-Fms antibody might be useful for inhibition of inflammation-induced bone erosion. In this study, we describe and discuss the effect the anti-c-Fms antibody has on pathological osteoclastogenesis and bone resorption.

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Macrophage colony-stimulating factor in patients with rheumatoid arthritis.

Cited by 26 publications

References 0 publications

SB1578, a Novel Inhibitor of JAK2, FLT3, and c-Fms for the Treatment of Rheumatoid Arthritis

SB1578, a Novel Inhibitor of JAK2, FLT3, and c-Fms for the Treatment of Rheumatoid Arthritis

Inhibition of colony-stimulating-factor-1 signalingin vivowith the orally bioavailable cFMS kinase inhibitor GW2580

Effect of Macrophage Colony-Stimulating Factor Receptor c-Fms Antibody on Lipopolysaccharide-Induced Pathological Osteoclastogenesis and Bone Resorption

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