title: Discoidin Domain Receptor 2 as a Potential Therapeutic Target for Development of Disease-Modifying Osteoarthritis Drugs.
abstract: Osteoarthritis (OA) is the most common form of arthritis disorders, but the identification of therapeutic targets to effectively prevent OA has been increasingly difficult. The goal of this investigation is to provide experimental evidence that discoidin domain receptor 2 (DDR2) may be an ideal target for the development of disease-modifying OA drugs. Ddr2 was conditionally deleted from articular cartilage of adult mouse knee joints. Aggrecan-CreERT2;floxed Ddr2 mice, which were generated by crossing Aggrecan-CreERT2 mice with floxed Ddr2 mice, then received tamoxifen injections at the age of 8 weeks. The mice were then subjected to destabilization of the medial meniscus (DMM) surgery. At 8 and 16 weeks after DMM, mice were euthanized for the collection of knee joints. In a separate experiment, Aggrecan-CreERT2;floxed Ddr2 mice were subjected to DMM at the age of 10 weeks. The mice then received tamoxifen injections at 8 weeks after DMM. The mice were euthanized for the collection of knee joints at 16 weeks after DMM. The progressive process of articular cartilage degeneration was significantly delayed in the knee joints of Ddr2-deficient mice in comparison to their control littermates. Articular cartilage damage in the knee joints of the mice was associated with increased expression profiles of both Ddr2 and matrix metalloproteinase 13. These findings suggest that DDR2 may be an ideal target for the development of disease-modifying OA drugs.
authors.affiliation: Department of Prosthodontics, Harvard School of Dental Medicine, Boston, Massachusetts.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Manning
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Faculty of Medicine, Harvard Medical School, Boston, Massachusetts. Electronic address: yefu_li@hms.harvard.edu.
authors.forename: Yefu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts.
authors.forename: Nithya S
authors.initials: NS
authors.lastname: Chickmagalur
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; State Key Laboratory of Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts; Faculty of Medicine, Harvard Medical School, Boston, Massachusetts. Electronic address: lin_xu@hms.harvard.edu.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D053674:Aggrecans / Q000235:genetics; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D000070820:Discoidin Domain Receptor 2 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007719:Knee Joint; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D008592:Menisci, Tibial / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D053674:Aggrecans; C000603242:Ddr2 protein, mouse; D000070820:Discoidin Domain Receptor 2; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse