Bartaloni, J.

Brandi, M.L.

Cagnoni, M.

Carossino, A.M.

Carossino, R.

Galli, G.

Gozzini, A.

Pinzani, P.

Piscitelli, E.

Recenti, R.

Simi, L.

Tanini, A.

Tognarini, I.

Zappoli, G.

Zonefrati, R.

Scientific Open-access Literature Archive and Repository

PROTECTIVE ACTION OF CLODRONATE ON OSTEOARTHRITIC CARTILAGER. Recenti1, A.M. Carossino1, R. Carossino1, E. Piscitelli2, A. Gozzini1, P. Pinzani2, L. Simi2, G. Galli1, I. Tognarini1, J. Bartaloni1, R. Zonefrati1, G. Zappoli1, A. Tanini1, M. Cagnoni1, M.L. Brandi11 Department of Internal Medicine, University of Florence, Florence, Italy2 Department of Clinical Physiopathology, University of Florence, Florence, ItalyBisphosphonates enhance bone mass and prevent bone resorption in patients affected by chronic inflam-matory and degenerative arthropaties. In details, in animal models, clodronate shows an anti-inflammato-ry effect and decreases cartilage damage. In patients with rheumatoid arthritis, clodronate decreasesplasma levels of proinflammatory factors secreted by synovial macrophages. Since a few informations about clodronate action on chondrocytes are available, we studied the effect ofclodronate (1 µM - 1 mM) on human articular chondrocytes from cartilage of osteoarthritic patients. Bio-logical and molecular effects of clodronate have been evaluated as follows: - Proliferation and viability bycell counting and Trypan Blue staining. - Apoptosis by chromosome ladder analysis and Hoechst 33342nuclear staining. - Mucopolysaccarides production by PAS reaction. - Metalloproteinases 9 (MMP9) andTIMP-1 expression by quantitative Real Time-PCR. - Intracellular ATP evaluation by chemoluminescentluciferase assay. - Osteoprotegerin (OPG) and RANK-Ligand (RANK-L) release by ELISA test on culturemedia. - Collagen I and II expression by Reverse Trascriptase-PCR and Real Time-PCR. Higher doses ofclodronate inhibit cellular proliferation and maintain >80% cell viability along 6 days of incubation. Cellnumber decrease was due to apoptotic events, as evidenced by chromosomic ladder and picnotic nuclearfragmentation (10% for 100 µM and 13% for 1 mM clodronate versus 5% of control). MMP9 expression isstrongly reduced while OPG and RANK-L release is not altered. Clodronate doesn’t affect mucopolysac-carides production. Intracellular ATP significantly increases in the presence of 10 µM of clodronate, whencompared to control (26.92±0.23% of increase). Collagen I and mainly collagen II expression are signifi-cantly enhanced after incubation with clodronate. These results show that clodronate acts on chondro-cytes promoting a protective and regenerative action on osteoarthrtitic cartilage.236 Clinical Cases in Mineral and Bone Metabolism 2005; 2(3): 185-252BSTR CT (V Congresso CCMBM)  18/11/2005  15.59  Pagina 236FOR REVIEW ONLY© CIC EDIZIONI INTERNAZIONALI

Protective action of clodronate on osteoarthritic cartilage

http://eprints.bice.rm.cnr.it/9049/1/article.pdf

Protective action of clodronate on osteoarthritic cartilage

Abstract

Similar works

Full text

Available Versions

Scientific Open-access Literature Archive and Repository