Chih-Chung Liu1,2, Hoong-Chien Lee3,4, Yi-Shian Peng3, Ailun Heather Tseng5, Jia-Lin Wu6,7, Wei-Yuan Tsai8, Chih-Shung Wong8,9, Li-Jen Su3. 1. Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan. 2. Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 3. Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan. 4. Department of Physics, Chung Yuan Christian University, Taoyuan, Taiwan. 5. Department of Surgery, Hsinchu Cathay General Hospital, Hsinchu, Taiwan. 6. Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 7. Department of Orthopedics, Taipei Medical University Hospital, Taipei, Taiwan. 8. Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwna. 9. Graduate Institute of Medical Sciences, National Defence Medical Center, Taipei, Taiwan.
Abstract
OBJECTIVE: The current therapeutic strategy for posttraumatic osteoarthritis (PTOA) focuses on early intervention to attenuate disease progression, preserve joint function, and defer joint replacement timing. Sequential transcriptomic changes of articular cartilage in a rat model were investigated to explore the molecular mechanism in early PTOA progression. DESIGN: Anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx)-induced PTOA model was applied on male Wistar rats. Articular cartilages were harvested at time 0 (naïve), 2 week, and 4 weeks after surgery. Affymetrix Rat genome 230 2.0 array was utilized to analyze the gene expression changes of articular cartilages. RESULTS: We identified 849 differentially expressed genes (DEGs) at 2 weeks and 223 DEGs at 4 weeks post-ACLT + MMx surgery compared with time 0 (naïve group). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to gain further insights from these DEGs. 22 novel genes and 1 novel KEGG pathway (axon guidance) in cartilage degeneration of osteoarthritis were identified. Axon guidance molecules-Gnai1, Sema4d, Plxnb1, and Srgap2 commonly dysregulated in PTOA progression. Gnai1 gene showed a concordant change in protein expression by immunohistochemistry staining. CONCLUSIONS: Our study identified 22 novel dysregulated genes and axon guidance pathway associated with articular cartilage degeneration in PTOA progression. These findings provide the potential candidates of biomarkers and therapeutic targets for further investigation.
OBJECTIVE: The current therapeutic strategy for posttraumatic osteoarthritis (PTOA) focuses on early intervention to attenuate disease progression, preserve joint function, and defer joint replacement timing. Sequential transcriptomic changes of articular cartilage in a rat model were investigated to explore the molecular mechanism in early PTOA progression. DESIGN: Anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx)-induced PTOA model was applied on male Wistar rats. Articular cartilages were harvested at time 0 (naïve), 2 week, and 4 weeks after surgery. Affymetrix Rat genome 230 2.0 array was utilized to analyze the gene expression changes of articular cartilages. RESULTS: We identified 849 differentially expressed genes (DEGs) at 2 weeks and 223 DEGs at 4 weeks post-ACLT + MMx surgery compared with time 0 (naïve group). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to gain further insights from these DEGs. 22 novel genes and 1 novel KEGG pathway (axon guidance) in cartilage degeneration of osteoarthritis were identified. Axon guidance molecules-Gnai1, Sema4d, Plxnb1, and Srgap2 commonly dysregulated in PTOA progression. Gnai1 gene showed a concordant change in protein expression by immunohistochemistry staining. CONCLUSIONS: Our study identified 22 novel dysregulated genes and axon guidance pathway associated with articular cartilage degeneration in PTOA progression. These findings provide the potential candidates of biomarkers and therapeutic targets for further investigation.
Authors: K W Finnson; W L Parker; Y Chi; C D Hoemann; M B Goldring; J Antoniou; A Philip Journal: Osteoarthritis Cartilage Date: 2010-09-15 Impact factor: 6.576
Authors: John M Dawes; Hannes Kiesewetter; James R Perkins; David L H Bennett; Stephen B McMahon Journal: Mol Pain Date: 2013-11-08 Impact factor: 3.395