Suppression of Adjuvant-Induced Arthritic Bone Destruction by Cyclooxygenase-2 Selective Agents With and Without Inhibitory Potency Against Carbonic Anhydrase II
| Autor: | Mika Katagiri, Hatsue Tazaki, Masao Sasamata, Aishi Kimoto, Shun-ichi Harada, Toru Ogasawara, Hiroshi Kawaguchi, Tsuyoshi Takato, Kazuto Hoshi, Daichi Chikazu, Masahiro Noguchi, Kozo Nakamura, Ung-il Chung, Hideto Akama |
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| Rok vydání: | 2005 |
| Předmět: |
Male
musculoskeletal diseases Endocrinology Diabetes and Metabolism Carbonic anhydrase II Osteoclasts Mice Inbred Strains Pharmacology Carbonic Anhydrase II Bone resorption Mice Adjuvants Immunologic In vivo Osteoclast Osteoarthritis medicine Animals Potency Cyclooxygenase Inhibitors Orthopedics and Sports Medicine Bone Resorption Carbonic Anhydrase Inhibitors Cyclooxygenase 2 Inhibitors biology Chemistry Cell Differentiation Rats medicine.anatomical_structure Biochemistry Eicosanoid Cyclooxygenase 2 Rats Inbred Lew Cyclooxygenase 1 biology.protein Cyclooxygenase Bone marrow |
| Zdroj: | Journal of Bone and Mineral Research. 21:219-227 |
| ISSN: | 0884-0431 |
| Popis: | In vitro assays revealed that COX-2 inhibitors with CA II inhibitory potency suppressed both differentiation and activity of osteoclasts, whereas that without the potency reduced only osteoclast differentiation. However, all COX-2 inhibitors similarly suppressed bone destruction in adjuvant-induced arthritic rats, indicating that suppression of osteoclast differentiation is more effective than that of osteoclast activity for the treatment. Introduction: Cyclooxygenase (COX)-2 and carbonic anhydrase II (CA II) are known to play important roles in the differentiation of osteoclasts and the activity of mature osteoclasts, respectively. Because several COX-2 selective agents were recently found to possess an inhibitory potency against CA II, this study compared the bone sparing effects of COX-2 selective agents with and without the CA II inhibitory potency. Materials and Methods: Osteoclast differentiation was determined by the mouse co-culture system of osteoblasts and bone marrow cells, and mature osteoclast activity was measured by the pit area on a dentine slice resorbed by osteoclasts generated and isolated from bone marrow cells. In vivo effects on arthritic bone destruction were determined by radiological and histological analyses of hind-paws of adjuvant-induced arthritic (AIA) rats. Results: CA II was expressed predominantly in mature osteoclasts, but not in the precursors. CA II activity was inhibited by sulfonamide-type COX-2 selective agents celecoxib and JTE-522 similarly to a CA II inhibitor acetazolamide, but not by a methylsulfone-type COX-2 inhibitor rofecoxib. In vitro assays clearly revealed that celecoxib and JTE-522 suppressed both differentiation and activity of osteoclasts, whereas rofecoxib and acetazolamide suppressed only osteoclast differentiation and activation, respectively. However, bone destruction in AIA rats was potently and similarly suppressed by all COX-2 selective agents whether with or without CA II inhibitory potency, although only moderately by acetazolamide. Conclusions: Suppression of osteoclast differentiation by COX-2 inhibition is more effective than suppression of mature osteoclast activity by CA II inhibition for the treatment of arthritic bone destruction. |
| Databáze: | OpenAIRE |
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