Strontium ranelate increases cartilage matrix formation.

Cartilage/drug effects/metabolism; Cells, Cultured; Chondrocytes/drug effects/metabolism; Extracellular Matrix/drug effects; Humans; Insulin-Like Growth Factor I/pharmacology; Interleukin-1/pharmacology; Matrix Metalloproteinase 3/biosynthesis/metabolism; Organometallic Compounds/pharmacology; Proteoglycans/metabolism; Thiophenes/pharmacology

Abstract :

[en] Based on previous studies showing that strontium ranelate (S12911) modulates bone loss in osteoporosis, it could be hypothesized that this drug also is effective on cartilage degradation in osteoarthritis (OA). This was investigated in vitro on normal and OA human chondrocytes treated or not treated with interleukin-1beta (IL-1beta). This model mimics, in vitro, the imbalance between chondroformation and chondroresorption processes observed in vivo in OA cartilage. Chondrocytes were isolated from cartilage by enzymatic digestion and cultured for 24-72 h with 10(-4)-10(-3) M strontium ranelate, 10(-3) M calcium ranelate, or 2 x 10(-3) M SrCl2 with or without IL-1beta or insulin-like growth factor I (IGF-I). Stromelysin activity and stromelysin quantitation were assayed by spectrofluorometry and enzyme amplified sensitivity immunoassay (EASIA), respectively. Proteoglycans (PG) were quantified using a radioimmunoassay. Newly synthesized glycosaminoglycans (GAGs) were quantified by labeled sulfate (Na2(35)SO4) incorporation. This method allowed the PG size after exclusion chromatography to be determined. Strontium ranelate, calcium ranelate, and SrCl2 did not modify stromelysin synthesis even in the presence of IL-1beta. Calcium ranelate induced stromelysin activation whereas strontium compounds were ineffective. Strontium ranelate and SrCl2 both strongly stimulated PG production suggesting an ionic effect of strontium independent of the organic moiety. Moreover, 10(-3) M strontium ranelate increased the stimulatory effect of IGF-I (10(-9) M) on PG synthesis but did not reverse the inhibitory effect of IL-1beta. Strontium ranelate strongly stimulates human cartilage matrix formation in vitro by a direct ionic effect without stimulating the chondroresorption processes. This finding provides a preclinical basis for in vivo testing of strontium ranelate in OA.

Disciplines :

Rheumatology

Author, co-author :

Henrotin, Yves

Labasse, Alain

Zheng, S. X.

Galais, P.

Tsouderos, Y.; Université de Liège - ULiège > Département des sciences de la motricité > Evaluation et entraînement des aptitudes physiques

Crielaard, Jean-Michel ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé

Reginster, Jean-Yves

Language :

English

Title :

Strontium ranelate increases cartilage matrix formation.

Publication date :

2001

Journal title :

Journal of Bone and Mineral Research

ISSN :

0884-0431

eISSN :

1523-4681

Publisher :

American Society for Bone and Mineral Research, Washington, United States - District of Columbia

Volume :

Issue :

Pages :

299-308

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 16 April 2011

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