Cartilage oligomeric matrix protein (COMP) is modified by intra-articular liposomal clodronate in an experimental model of arthritis.
OBJECTIVE
High-dose liposomal bisphosphonates exert apoptotic effects. This work studies the chondroprotective and anti-inflammatory properties of intra-articularly administered low-dose, non-cytotoxic liposomal clodronate.


METHODS
Antigen induced arthritis in rabbits was treated with intra-articular injections of liposomal clodronate. Drug effects on cartilage oligomeric matrix protein COMP was assessed using immunohistochemistry and morphometry of synovial membrane and hyaline articular cartilage.


RESULTS
COMP remained close to normal in liposomal clodronate treated superficial articular cartilage compared to a significant loss of COMP in arthritis controls treated with empty liposomes. The middle and deep layers of the hyaline articular cartilage were characterized by highly increased COMP expression in liposomal clodronate treated AIA joints compared to controls. In contrast to cartilage, synovial COMP expression was slightly decreased as a result of liposomal clodronate treatment.


CONCLUSIONS
Low-dose, non-cytotoxic liposomal clodronate exerts a dichotomous effect on synovial membrane and articular cartilage COMP in the AIA model. COMP is a useful inflammation marker in the synovial tissue, but it also contributes to the structural integrity of the hyaline articular cartilage forming bridges between type II and IX collagens. Enhancement of COMP in clodronate treated AIA cartilage suggests a chondroprotective and anti-inflammatory effect in the inflammatorily damaged and mechanically strained cartilage.
Gomez-Barrena
E
E
Bone and Joint Research Laboratory, Fundación Jiménez Díaz Hospital, Autónoma University of Madrid, Spain. egomez@fjd.es
Lindroos
L
L
Ceponis
A
A
López-Franco
M
M
Sanchez-Pernaute
O
O
Mönkkönen
J
J
Salo
J
J
Herrero-Beaumont
G
G
Konttinen
Y
Y
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004002:Clodronic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D007270:Injections, Intra-Articular; D008081:Liposomes; D064235:Matrilin Proteins; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D050071:Bone Density Conservation Agents; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D008081:Liposomes; D064235:Matrilin Proteins; D004002:Clodronic Acid