scholarly journals Anti-interleukin-6 receptor antibody prevents systemic bone mass loss via reducing the number of osteoclast precursors in bone marrow in a collagen-induced arthritis model

2014 ◽  
Vol 175 (2) ◽  
pp. 172-180 ◽  
Author(s):  
Keisuke Tanaka ◽  
Misato Hashizume ◽  
Masahiko Mihara ◽  
Hiroto Yoshida ◽  
Miho Suzuki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Mass Loss ◽  
Interleukin 6 ◽  
Collagen Induced Arthritis ◽  
Arthritis Model ◽  
Bone Mass Loss ◽  
Receptor Antibody ◽  
Osteoclast Precursors ◽  
Interleukin 6 Receptor

scholarly journals A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis

2009 ◽  
Vol 11 (6) ◽  
pp. R185 ◽  
Author(s):  
Benoit Le Goff ◽  
Elise Soltner ◽  
Céline Charrier ◽  
Yves Maugars ◽  
Françoise Rédini ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Mass ◽  
Mass Loss ◽  
Collagen Induced Arthritis ◽  
Bone Mass Loss ◽  
Bone Erosions

Imaging of lesions in a murine rheumatoid arthritis model with a humanized anti-interleukin-6 receptor antibody

2005 ◽  
Vol 19 (4) ◽  
pp. 261-266 ◽  
Author(s):  
Kanji Sugimoto ◽  
Norihiro Nishimoto ◽  
Tadamitsu Kishimoto ◽  
Kazuyuki Yoshizaki ◽  
Tsunehiko Nishimura
Keyword(s):  
Rheumatoid Arthritis ◽  
Interleukin 6 ◽  
Arthritis Model ◽  
Receptor Antibody ◽  
Interleukin 6 Receptor

scholarly journals Tocilizumab, a Humanized Anti-interleukin-6 Receptor Antibody, Ameliorates Joint Swelling in Established Monkey Collagen-Induced Arthritis

2008 ◽  
Vol 31 (6) ◽  
pp. 1159-1163 ◽  
Author(s):  
Yasushi Uchiyama ◽  
Keigo Yorozu ◽  
Misato Hashizume ◽  
Yoichiro Moriya ◽  
Masahiko Mihara
Keyword(s):  
Interleukin 6 ◽  
Collagen Induced Arthritis ◽  
Receptor Antibody ◽  
Interleukin 6 Receptor

Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats

2021 ◽  
pp. 153537022110110
Author(s):  
Yu-Ting Cheng ◽  
Jian Liao ◽  
Qian Zhou ◽  
Hua Huo ◽  
Lucas Zellmer ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Mass ◽  
Mass Loss ◽  
Ovariectomized Rats ◽  
Therapeutic Effects ◽  
Bone Mass Loss ◽  
Cellular Effects ◽  
Protein Levels ◽  
Adverse Factor ◽  
Osteoclast Apoptosis

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.

scholarly journals GPR109A mediates the effects of hippuric acid on regulating osteoclastogenesis and bone resorption in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jin-Ran Chen ◽  
Haijun Zhao ◽  
Umesh D. Wankhade ◽  
Sree V. Chintapalli ◽  
Can Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Mass ◽  
Hippuric Acid ◽  
Ex Vivo ◽  
Marrow Cell ◽  
Osteoclast Differentiation ◽  
Bone Homeostasis ◽  
Wild Type ◽  
Osteoclast Precursors

AbstractThe G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A−/−) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A−/− mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A−/− mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A−/− mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/β-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/β-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A−/− mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.

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