Demographic, clinical and therapeutic data at the time of an enrollment in IORRA.

<p>*Maximum value of RF measured in the cohort project during 2000–2010 for each individual was used.</p>†<p>Cut-off  = 4.5 IU/ml.</p><p>IORRA, Institute of Rheumatology Rheumatoid Arthritis cohort study; BMI, body mass index; DAS28, disease activity score in 28 joints; J-HAQ, the Japanese version of Health Assessment Questionnaire; RF, rheumatoid factor; ACPA, anti-citrullinated peptide antibody; TKR, total knee replacement; DMARDs, disease modifying antirheumatic drugs.</p

Inhibition of IL-23-induced osteoclastogenesis by osteoprotegerin, anti-IL-17 antibody, and etanercept

<p><b>Copyright information:</b></p><p>Taken from "IL-23 induces human osteoclastogenesis via IL-17 , and anti-IL-23 antibody attenuates collagen-induced arthritis in rats"</p><p>http://arthritis-research.com/content/9/5/R96</p><p>Arthritis Research & Therapy 2007;9(5):R96-R96.</p><p>Published online 23 Sep 2007</p><p>PMCID:PMC2212562.</p><p></p> Peripheral blood mononuclear cells (PBMC) were cultured during the first 3 days with macrophage-colony stimulating factor (M-CSF) and recombinant human (rh)IL-23 (1.0 ng/ml) . At the same time, osteoprotegerin (OPG, 250 ng/ml) , anti-IL-17 antibody (5 μg/ml) , or etanercept (0.01 μg/ml) was added with rhIL-23 (1.0 ng/ml). Adherent cells were cultured with M-CSF alone during the last 7 days (days 4 to 10 ). As controls, PBMC were cultured with M-CSF alone during the first 3 days, after which adherent cells were cultured with M-CSF only (negative control) or with soluble receptor activator of NF-κB ligand (sRANKL; 100 ng/ml) (positive control). Osteoclasts were detected by immunohistological staining for vitronectin receptor αvβ3 (CD51/61). Original magnification ×100

IL-23-induced osteoclastogenesis from cultured human peripheral blood mononuclear cells

<p><b>Copyright information:</b></p><p>Taken from "IL-23 induces human osteoclastogenesis via IL-17 , and anti-IL-23 antibody attenuates collagen-induced arthritis in rats"</p><p>http://arthritis-research.com/content/9/5/R96</p><p>Arthritis Research & Therapy 2007;9(5):R96-R96.</p><p>Published online 23 Sep 2007</p><p>PMCID:PMC2212562.</p><p></p> A variable concentration of recombinant human (rh)IL-23 (0.01, 0.1, or 1 ng/ml) was present during the first 3 days (days 0 to 4). After 10 days, osteoclasts positive for anti-vitronectin receptor antibody were counted. Data are expressed as means and SD for triplicate cultures. Experiments were repeated three times with similar, significant results; = 0.002 (Student's test)

Variation in degree of inflammation of rat paws after treatment with vehicle or IL-23 blockade

<p><b>Copyright information:</b></p><p>Taken from "IL-23 induces human osteoclastogenesis via IL-17 , and anti-IL-23 antibody attenuates collagen-induced arthritis in rats"</p><p>http://arthritis-research.com/content/9/5/R96</p><p>Arthritis Research & Therapy 2007;9(5):R96-R96.</p><p>Published online 23 Sep 2007</p><p>PMCID:PMC2212562.</p><p></p> Photographs showing paws of rats with collagen-induced arthritis (CIA) that were treated with vehicle or anti-IL-23 antibody on day 21. Control rats. Rats with CIA that were treated with vehicle. Rats with CIA that were treated with anti-IL-23 antibody (3.0 μg) from day 14. Slides stained with hematoxylin and eosin representing synovial tissues obtained from right paws on day 28. Control rats. Rats with CIA that were treated with vehicle. Rats with CIA that were treated with anti-IL-23 antibody (3.0 μg) from day 14. Original magnification ×100

Variation in paw volume in rats with CIA treated with vehicle or IL-23 blockade

<p><b>Copyright information:</b></p><p>Taken from "IL-23 induces human osteoclastogenesis via IL-17 , and anti-IL-23 antibody attenuates collagen-induced arthritis in rats"</p><p>http://arthritis-research.com/content/9/5/R96</p><p>Arthritis Research & Therapy 2007;9(5):R96-R96.</p><p>Published online 23 Sep 2007</p><p>PMCID:PMC2212562.</p><p></p> Paw volumes of control rats, vehicle-treated rats with collagen-induced arthritis (CIA), and rats with CIA that were treated with anti-IL-23 antibody, from day 0 to day 21. Open squares, rats with CIA treated with vehicle; open circles, controls; filled triangles, rats with CIA treated with 3.0 μg of anti-IL-23 antibody; filled diamonds, rats with CIA treated with 6.0 μg of anti-IL-23 antibody. Means ± SD are shown. = 0.021 versus controls, = 0.021 versus controls, = 0.014 versus vehicle, = 0.007 versus vehicle (Mann–Whitney test). Arthritis scores of control rats, vehicle-treated rats with CIA, and rats with CIA that were treated with anti-IL-23 antibody, from day 0 to day 28. Open squares, rats with CIA treated with vehicle; open circles, controls; filled triangles, rats with CIA treated with 3.0 μg of anti-IL-23 antibody; filled diamonds, rats with CIA treated with 6.0 μg of anti-IL-23 antibody. Means ± SD are shown. = 0.021 versus controls, = 0.021 versus controls (Mann–Whitney test)

Cumulative incidence of hip fracture for patients who were homo- or heterozygous for the non-risk allele and patients homozygous for the risk allele of each single nucleotide polymorphism (by the Kaplan-Meier method).

<p>Homozygous for the risk allele of rs6993813 (C) in the <i>OPG</i> locus was significantly associated with the occurrence of hip fracture (<i>P</i> = 0.0067).</p

Typical radiographic images obtained on day 28, showing differences in paws

<p><b>Copyright information:</b></p><p>Taken from "IL-23 induces human osteoclastogenesis via IL-17 , and anti-IL-23 antibody attenuates collagen-induced arthritis in rats"</p><p>http://arthritis-research.com/content/9/5/R96</p><p>Arthritis Research & Therapy 2007;9(5):R96-R96.</p><p>Published online 23 Sep 2007</p><p>PMCID:PMC2212562.</p><p></p> The groups were control rats, vehicle-treated rats with collagen-induced arthritis (CIA), and rats with CIA treated with anti-IL-23 antibody on day 28. Frontal views; lateral views. Control rats. Rats with CIA treated with vehicle. Rats with CIA treated with anti-IL-23 antibody (3.0 μg) from day 14. Note that rats wth CIA treated with vehicle showed radiographic changes characterized by bone erosion and joint space narrowing

IL-23-induced formation of human osteoclasts from peripheral blood mononuclear cells (PBMC)

<p><b>Copyright information:</b></p><p>Taken from "IL-23 induces human osteoclastogenesis via IL-17 , and anti-IL-23 antibody attenuates collagen-induced arthritis in rats"</p><p>http://arthritis-research.com/content/9/5/R96</p><p>Arthritis Research & Therapy 2007;9(5):R96-R96.</p><p>Published online 23 Sep 2007</p><p>PMCID:PMC2212562.</p><p></p> PBMC were cultured in the presence of macrophage-colony stimulating factor (M-CSF) and recombinant human (rh)IL-23 (0.01, 0.1, 1.0, 10, 100, or 200 ng/ml) during the first 3 days. Adherent cells were then cultured with M-CSF alone during the last 7 days (days 4 to 10 as indicated). Original magnification ×100

IL-23-induced IL-17 production by activated human T cells in a dose-dependent manner

<p><b>Copyright information:</b></p><p>Taken from "IL-23 induces human osteoclastogenesis via IL-17 , and anti-IL-23 antibody attenuates collagen-induced arthritis in rats"</p><p>http://arthritis-research.com/content/9/5/R96</p><p>Arthritis Research & Therapy 2007;9(5):R96-R96.</p><p>Published online 23 Sep 2007</p><p>PMCID:PMC2212562.</p><p></p> Human CD3-positive T cells were cultured in the absence or presence of recombinant human (rh)IL-23 (1.0 or 3.0 ng/ml). After 48 hours, secretion of IL-17 in the cell culture supernatant was assayed by ELISA. Results for one representative donor are presented here and are expressed as means and SD. ELISA measurement of IL-17 production by human CD3-positive T cells treated for 48 hours with various concentrations of rhIL-23 (1.0, 3.0, or 10 ng/ml) in the presence or absence of plate-bound anti-CD3 and anti-CD28, for five representative donors. Data are expressed as means and SD. = 0.009 versus non–activated T cells (Mann–Whitney test). ELISA measurement of IFN-γ production by human CD3-positive T cells treated for 48 hours with various concentrations of rhIL-23 (1.0, 3.0, or 10 ng/ml) in the presence or absence of plate-bound anti-CD3 and anti-CD28, for four representative donors. Data are expressed as means and SD. 0.02 versus non–activated T cells Mann–Whitney test). Ratio of the production levels of IL-17 to those of IFN-γ (IL-17/IFN-γ) calculated from levels of IL-17 or IFN-γ produced from activated CD3-positive T cells at each concentration of rhIL-23 (0, 1, 3, or 10 ng/ml)

Multivariate Cox proportional hazards model of each SNP associated with the occurrence of hip fracture.

<p>All analyses were adjusted for independent non-genetic factors: age, body mass index, Japanese version of Health Assessment Questionnaire disability score, and history of total knee replacement. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104587#pone.0104587-Furuya1" target="_blank">[7]</a>.</p><p>*Alleles are listed as major allele/minor allele.</p><p>SNP, single nucleotide polymorphism; MAF, minor allele frequency; HR, hazard ratio; CI, confidence interval; <i>OPG</i>, osteoprotegerin; <i>ZBTB40</i>, zinc finger and BTB domain containing 40; <i>MHC</i>, major histocompatibility complex; <i>RANK</i>, receptor activator of the nuclear factor-κB; <i>SPTBN1</i>, spectrin β nonerythrocytic 1; <i>LRP4</i>, low-density lipoprotein receptor-related protein 4.</p