title: Kartogenin treatment prevented joint degeneration in a rodent model of osteoarthritis: A pilot study.
abstract: Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end-stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra-articular injection of 125 μM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T1ρand T2) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX-I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro-computed tomography (micro-CT) and histology. KGN treatment significantly lowered the T1ρand T2relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX-I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post-traumatic OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1780-1789, 2016.
authors.affiliation: Musculoskeletal Quantitative Imaging Research, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California. gemohan@ucdavis.edu.|Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California. gemohan@ucdavis.edu.
authors.forename: Geetha
authors.initials: G
authors.lastname: Mohan
authors.affiliation: Musculoskeletal Quantitative Imaging Research, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California.
authors.forename: Sergey
authors.initials: S
authors.lastname: Magnitsky
authors.affiliation: Department of Medical Imaging, Ottawa Hospital, Ottawa, Ontario, Canada.
authors.forename: Gerd
authors.initials: G
authors.lastname: Melkus
authors.affiliation: Singapore University of Technology and Design, Singapore.
authors.forename: Karupppasamy
authors.initials: K
authors.lastname: Subburaj
authors.affiliation: Musculoskeletal Quantitative Imaging Research, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California.
authors.forename: Galateia
authors.initials: G
authors.lastname: Kazakia
authors.affiliation: Musculoskeletal Quantitative Imaging Research, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Burghardt
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, California.
authors.forename: Alexis
authors.initials: A
authors.lastname: Dang
authors.affiliation: Department of Internal Medicine, University of California at Davis Medical Center, Sacramento, California.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Lane
authors.affiliation: Musculoskeletal Quantitative Imaging Research, Department of Radiology and Biomedical Imaging, University of California, San Francisco, California.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002358:Cartilage, Articular / Q000187:drug effects*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D008279:Magnetic Resonance Imaging; D008297:Male; D010003:Osteoarthritis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010795:Phthalic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
chemical_list: D000813:Anilides; D015415:Biomarkers; D010795:Phthalic Acids; C572342:kartogenin
keywords: 7T MRI; Osteoarthritis; cartilage; kartogenin; subchondral bone