Strontium Ranelate Increases Cartilage Matrix Formation

Abstract

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-1␤ (IL-1␤). 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 ⅐ 10 ؊3 M SrCl 2 with or without IL-1␤ 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 (Na 2 35 SO 4 ) incorporation. This method allowed the PG size after exclusion chromatography to be determined. Strontium ranelate, calcium ranelate, and SrCl 2 did not modify stromelysin synthesis even in the presence of IL-1␤. Calcium ranelate induced stromelysin activation whereas strontium compounds were ineffective. Strontium ranelate and SrCl 2 both strongly stimulated PG production suggesting an ionic effect of strontium independent of the organic moiety.

Histological and Histomorphometric Study of the Effect of Strontium Ranelate on the Healing of One-Wall Intrabony Periodontal Defects in Dogs

“…In vitro studies revealed that SrRan has an anabolic and antiresorptive activity, which increase both the collagen and non-collagen protein synthesis [4,5], enhance pre-osteoblast differentiation [6,7], inhibit osteoclast differentiation, and function [8,9].…”

Pathogenesis of Osteoarthritis and Substantiation of the Use of Strontium Ranelate

“…П р о г р е с с в р е в м а т о л о г и и в X X I в е к е представили данные лабораторного исследования, в кото-ром СР усиливал формирование хрящевого матрикса [50]. При этом было отмечено увеличение синтеза высокомоле-кулярных протеогликанов как в нормальном суставном хряще (р<0,001), так и при ОА (р=0,02).…”

Pharmacological Treatment of Osteoporosis

“…These findings suggest that strontium ranelate stimulates human cartilage matrix formation in vitro without activating the chondroresorption process. (Henrotin et al, 2001) …”