Reversible depletion of synovial lining cells after intra-articular treatment with liposome-encapsulated dichloromethylene diphosphonate. 1993

P L van Lent, and L van den Bersselaar, and A E van den Hoek, and M van de Ende, and C D Dijkstra, and N van Rooijen, and L B van de Putte, and W B van den Berg
Department of Rheumatology, University Hospital St. Radboud, Nijmegen, The Netherlands.

We studied the depletion and repopulation of synovial lining cells in mice. A single intra-articular injection of liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP) in the mouse knee joint caused selective elimination of synovial lining cells. Depletion of cells occurred within a few days as evidenced by light microscopic, electronmicroscopic and immunohistochemical studies. Maximal depletion was seen on day 7. Repopulation was observed in the following weeks, starting at the bone side of the joint. Until day 30, full recovery (60% recovery) was not observed in the lining lying adjacent to the dermis. Side effects on cartilage metabolism, such as inhibition of proteoglycan synthesis or degradation of proteoglycans from the matrix was minor but significant, 1 and 2 days after liposome treatment but thereafter full recovery was observed. Selective elimination of lining cells from the joint enabled us to study the in vivo role of these cells in the onset and subsequent pathology of experimental arthritis. An immune-complex-mediated experimental arthritis elicited in lining cell depleted joints that had received CL2MDP-liposomes 7 days earlier prevented inflammation as compared to controls.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007270 Injections, Intra-Articular Methods of delivering drugs into a joint space. Intra Articular Injection,Intraarticular Injection,Injections, Intraarticular,Intra-Articular Injections,Intraarticular Injections,Articular Injection, Intra,Articular Injections, Intra,Injection, Intra Articular,Injection, Intra-Articular,Injection, Intraarticular,Injections, Intra Articular,Intra Articular Injections,Intra-Articular Injection
D007719 Knee Joint A synovial hinge connection formed between the bones of the FEMUR; TIBIA; and PATELLA. Superior Tibiofibular Joint,Joint, Knee,Joint, Superior Tibiofibular,Knee Joints,Superior Tibiofibular Joints,Tibiofibular Joint, Superior
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D002358 Cartilage, Articular A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact. Articular Cartilage,Articular Cartilages,Cartilages, Articular
D004002 Clodronic Acid A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification. Clodronate,Dichloromethylene Diphosphonate,Bonefos,Cl2MDP,Clodronate Disodium,Clodronate Sodium,Dichloromethane Diphosphonate,Dichloromethanediphosphonate,Dichloromethanediphosphonic Acid,Dichloromethylene Biphosphonate,Dichloromethylenebisphosphonate,Acid, Clodronic,Acid, Dichloromethanediphosphonic,Biphosphonate, Dichloromethylene,Diphosphonate, Dichloromethane,Diphosphonate, Dichloromethylene,Disodium, Clodronate,Sodium, Clodronate
D004337 Drug Carriers Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers. Drug Carrier

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