Inhibition of bone resorption blunts osteoarthritis in mice with high bone remodelling.
BACKGROUND
Osteoarthritis (OA) is characterised by cartilage degradation and bone lesions. Subchondral bone may be involved in the pathogenesis of cartilage matrix breakdown.


OBJECTIVE
To assess the role of bone remodelling in OA by studying the effect of bisphosphonate on OA development in mice with high bone remodelling.


METHODS
Mice overexpressing Runx2 (Runx2-Tg) under the control of collagen type I that displayed high bone remodelling were used. Joint instability was performed by partial medial meniscectomy to induce OA.


RESULTS
Six weeks after surgery, tibial cartilage of Runx2-Tg mice displayed an increased number of ADAMTS-4- and ADAMTS-5-expressing chondrocytes compared with controls (p<0.05). This increase was higher in Runx2-Tg mice than in wild-type mice, although their OA score did not differ (2.5+/-0.6 vs 2.4+/-0.2, P=NS). Pamidronate reduced the OA score in Runx2-Tg mice but not in wild-type littermates (1.2+/-0.5 vs 2.7+/-0.4; p<0.05) despite the reduction of bone resorption and of the expression of cartilage proteases in both genotypes.


CONCLUSIONS
These findings support the hypothesis that the level of bone resorption influences cartilage metabolism and that inhibition might prevent the progression of OA. Targeting bone resorption might therefore provide an approach to the treatment of high bone resorbing forms of OA.
INSERM U606, Centre Viggo Petersen and Université Paris-Diderot Paris 7, Hôpital Lariboisière, 2 rue Ambroise Paré, Paris 75010, France.
Abderrahim
A
Kadri
Thomas
T
Funck-Brentano
Hilène
H
Lin
Hang-Korng
HK
Ea
Didier
D
Hannouche
Caroline
C
Marty
Frédéric
F
Lioté
Valérie
V
Geoffroy
Martine E
ME
Cohen-Solal
D051722:ADAM Proteins / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D004838:Epiphyses / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008592:Menisci, Tibial / Q000601:surgery; D051379:Mice; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D000077268:Pamidronate; D011509:Proteoglycans / Q000378:metabolism
D050071:Bone Density Conservation Agents; D050659:Core Binding Factor Alpha 1 Subunit; D004164:Diphosphonates; D011509:Proteoglycans; C493716:Runx2 protein, mouse; D051722:ADAM Proteins; D000077268:Pamidronate