Antiinflammatory and chondroprotective effects of the aminobisphosphonate incadronate (YM175) in adjuvant induced arthritis

Atsushi Matsuo, Toshihide Shuto, Go Hirata, Hideshi Satoh, Yoshihiro Matsumoto, Hongpu Zhao, Yukihide Iwamoto

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objective. Incadronate is a third-generation bisphosphonate that suppresses bone resorption and is used to treat skeletal disorders and prevent bone loss in pathological conditions. We evaluated its therapeutic potential and antiinflammatory effects in established adjuvant induced arthritis (AIA), a rat model of rheumatoid arthritis (RA). Methods. Rats were administered incadronate subcutaneously at a dose of either 0.1 or 1.0 mg/kg/day, or 0.1 or 1.0 mg/kg/week, while a positive control group received phosphate buffered saline alone from Day 14 (after the onset of arthritis) to Day 42. The destruction of bone and cartilage and the antiinflammatory effects of incadronate in rats with established AIA were assessed during treatment, with reference to the arthritis index, hind paw volume, and radiological and histological examinations. To establish whether incadronate affects the migration of inflammatory cells, a chemotaxis assay was carried out using macrophage-like RAW 264.7 cells. Results. In vivo, incadronate suppressed the clinical manifestations of AIA in a dose-dependent manner. In vitro, the various concentrations of incadronate suppressed the migration of macrophages, but the viability and adhesion of these cells were not suppressed. Conclusion. Incadronate not only inhibits bone destruction but also reduces cartilage degeneration and joint inflammation in rats with established AIA. The mechanism underlying these antiinflammatory actions of incadronate may be attributable to the inhibition of macrophage migration to the site of inflammation. Bisphosphonates might be effective in preventing the progressive joint destruction and inflammation seen in patients with RA.

Original languageEnglish
Pages (from-to)1280-1290
Number of pages11
JournalJournal of Rheumatology
Volume30
Issue number6
Publication statusPublished - Jun 1 2003
Externally publishedYes

Fingerprint

Experimental Arthritis
Anti-Inflammatory Agents
Macrophages
Diphosphonates
Inflammation
Bone and Bones
Arthritis
Cartilage
Rheumatoid Arthritis
Joints
cimadronate
Chemotaxis
Bone Resorption
Cell Adhesion
Cell Movement
Cell Survival
Phosphates
Control Groups
Therapeutics

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Antiinflammatory and chondroprotective effects of the aminobisphosphonate incadronate (YM175) in adjuvant induced arthritis. / Matsuo, Atsushi; Shuto, Toshihide; Hirata, Go; Satoh, Hideshi; Matsumoto, Yoshihiro; Zhao, Hongpu; Iwamoto, Yukihide.

In: Journal of Rheumatology, Vol. 30, No. 6, 01.06.2003, p. 1280-1290.

Research output: Contribution to journalArticle

Matsuo, Atsushi ; Shuto, Toshihide ; Hirata, Go ; Satoh, Hideshi ; Matsumoto, Yoshihiro ; Zhao, Hongpu ; Iwamoto, Yukihide. / Antiinflammatory and chondroprotective effects of the aminobisphosphonate incadronate (YM175) in adjuvant induced arthritis. In: Journal of Rheumatology. 2003 ; Vol. 30, No. 6. pp. 1280-1290.
@article{f883c7bcf6ee42739706777b521ef2dc,
title = "Antiinflammatory and chondroprotective effects of the aminobisphosphonate incadronate (YM175) in adjuvant induced arthritis",
abstract = "Objective. Incadronate is a third-generation bisphosphonate that suppresses bone resorption and is used to treat skeletal disorders and prevent bone loss in pathological conditions. We evaluated its therapeutic potential and antiinflammatory effects in established adjuvant induced arthritis (AIA), a rat model of rheumatoid arthritis (RA). Methods. Rats were administered incadronate subcutaneously at a dose of either 0.1 or 1.0 mg/kg/day, or 0.1 or 1.0 mg/kg/week, while a positive control group received phosphate buffered saline alone from Day 14 (after the onset of arthritis) to Day 42. The destruction of bone and cartilage and the antiinflammatory effects of incadronate in rats with established AIA were assessed during treatment, with reference to the arthritis index, hind paw volume, and radiological and histological examinations. To establish whether incadronate affects the migration of inflammatory cells, a chemotaxis assay was carried out using macrophage-like RAW 264.7 cells. Results. In vivo, incadronate suppressed the clinical manifestations of AIA in a dose-dependent manner. In vitro, the various concentrations of incadronate suppressed the migration of macrophages, but the viability and adhesion of these cells were not suppressed. Conclusion. Incadronate not only inhibits bone destruction but also reduces cartilage degeneration and joint inflammation in rats with established AIA. The mechanism underlying these antiinflammatory actions of incadronate may be attributable to the inhibition of macrophage migration to the site of inflammation. Bisphosphonates might be effective in preventing the progressive joint destruction and inflammation seen in patients with RA.",
author = "Atsushi Matsuo and Toshihide Shuto and Go Hirata and Hideshi Satoh and Yoshihiro Matsumoto and Hongpu Zhao and Yukihide Iwamoto",
year = "2003",
month = "6",
day = "1",
language = "English",
volume = "30",
pages = "1280--1290",
journal = "Journal of Rheumatology",
issn = "0315-162X",
publisher = "Journal of Rheumatology",
number = "6",

}

TY - JOUR

T1 - Antiinflammatory and chondroprotective effects of the aminobisphosphonate incadronate (YM175) in adjuvant induced arthritis

AU - Matsuo, Atsushi

AU - Shuto, Toshihide

AU - Hirata, Go

AU - Satoh, Hideshi

AU - Matsumoto, Yoshihiro

AU - Zhao, Hongpu

AU - Iwamoto, Yukihide

PY - 2003/6/1

Y1 - 2003/6/1

N2 - Objective. Incadronate is a third-generation bisphosphonate that suppresses bone resorption and is used to treat skeletal disorders and prevent bone loss in pathological conditions. We evaluated its therapeutic potential and antiinflammatory effects in established adjuvant induced arthritis (AIA), a rat model of rheumatoid arthritis (RA). Methods. Rats were administered incadronate subcutaneously at a dose of either 0.1 or 1.0 mg/kg/day, or 0.1 or 1.0 mg/kg/week, while a positive control group received phosphate buffered saline alone from Day 14 (after the onset of arthritis) to Day 42. The destruction of bone and cartilage and the antiinflammatory effects of incadronate in rats with established AIA were assessed during treatment, with reference to the arthritis index, hind paw volume, and radiological and histological examinations. To establish whether incadronate affects the migration of inflammatory cells, a chemotaxis assay was carried out using macrophage-like RAW 264.7 cells. Results. In vivo, incadronate suppressed the clinical manifestations of AIA in a dose-dependent manner. In vitro, the various concentrations of incadronate suppressed the migration of macrophages, but the viability and adhesion of these cells were not suppressed. Conclusion. Incadronate not only inhibits bone destruction but also reduces cartilage degeneration and joint inflammation in rats with established AIA. The mechanism underlying these antiinflammatory actions of incadronate may be attributable to the inhibition of macrophage migration to the site of inflammation. Bisphosphonates might be effective in preventing the progressive joint destruction and inflammation seen in patients with RA.

AB - Objective. Incadronate is a third-generation bisphosphonate that suppresses bone resorption and is used to treat skeletal disorders and prevent bone loss in pathological conditions. We evaluated its therapeutic potential and antiinflammatory effects in established adjuvant induced arthritis (AIA), a rat model of rheumatoid arthritis (RA). Methods. Rats were administered incadronate subcutaneously at a dose of either 0.1 or 1.0 mg/kg/day, or 0.1 or 1.0 mg/kg/week, while a positive control group received phosphate buffered saline alone from Day 14 (after the onset of arthritis) to Day 42. The destruction of bone and cartilage and the antiinflammatory effects of incadronate in rats with established AIA were assessed during treatment, with reference to the arthritis index, hind paw volume, and radiological and histological examinations. To establish whether incadronate affects the migration of inflammatory cells, a chemotaxis assay was carried out using macrophage-like RAW 264.7 cells. Results. In vivo, incadronate suppressed the clinical manifestations of AIA in a dose-dependent manner. In vitro, the various concentrations of incadronate suppressed the migration of macrophages, but the viability and adhesion of these cells were not suppressed. Conclusion. Incadronate not only inhibits bone destruction but also reduces cartilage degeneration and joint inflammation in rats with established AIA. The mechanism underlying these antiinflammatory actions of incadronate may be attributable to the inhibition of macrophage migration to the site of inflammation. Bisphosphonates might be effective in preventing the progressive joint destruction and inflammation seen in patients with RA.

UR - http://www.scopus.com/inward/record.url?scp=0038657557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038657557&partnerID=8YFLogxK

M3 - Article

C2 - 12784404

AN - SCOPUS:0038657557

VL - 30

SP - 1280

EP - 1290

JO - Journal of Rheumatology

JF - Journal of Rheumatology

SN - 0315-162X

IS - 6

ER -