Local removal of phagocytic synovial lining cells by clodronate-liposomes decreases cartilage destruction during collagen type II arthritis.
OBJECTIVE
To investigate whether local removal of phagocytic synovial lining cells (SLCs) from the knee joint before onset of collagen type II arthritis has an effect on development of cartilage destruction.


METHODS
Phagocytic SLCs were selectively depleted by a single injection of clodronate laden liposomes in the knee joint seven days before induction of collagen type II arthritis (CIA). Clodronate laden liposomes were given in one knee joint either alone or in combination with a short-term oral treatment of dexamethasone. Cartilage damage including proteoglycan depletion and chondrocyte death was measured in total knee joints sections stained with safranin-o or haematoxylin.


RESULTS
Local removal of phagocytic SLCs, seven days before arthritis onset, prevented cell influx for the larger part. Chondrocyte death was significantly decreased in the SLC depleted arthritic joint both at an early (6 days) and late (12 days) time point after CIA induction. However, depletion of proteoglycans from femoral and patellar cartilage layers was not prevented. If the mild acute inflammation caused by a single clodronate laden liposome injection in the left knee joint, was blocked by a short-term (on consecutive days 9, 8, 7, 6, 5 before CIA onset) oral treatment with dexamethasone, cell influx, but also proteoglycan depletion was almost completely blocked. In the contralateral control right knee joint prominent cell influx and severe cartilage damage was observed, indicating that there was no effect of dexamethasone anymore at the onset of CIA.


CONCLUSIONS
This study shows that removal of phagocytic lining cells before CIA induction, particularly in the presence of a short-term treatment with dexamethasone, decreases cartilage destruction.
Van Lent
P L
PL
Department of Rheumatology, University Hospital Nijmegen, the Netherlands.
Holthuysen
A E
AE
Van Rooijen
N
N
Van De Putte
L B
LB
Van Den Berg
W B
WB
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D004002:Clodronic Acid / Q000494:pharmacology*; D003094:Collagen; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000627:therapeutic use; D006614:Hindlimb; D007270:Injections, Intra-Articular; D008081:Liposomes; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010586:Phagocytes / Q000187:drug effects*; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology
D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D008081:Liposomes; D004002:Clodronic Acid; D003907:Dexamethasone; D003094:Collagen