title: Ameliorative effects of PACAP against cartilage degeneration. Morphological, immunohistochemical and biochemical evidence from in vivo and in vitro models of rat osteoarthritis.
abstract: Osteoarthritis (OA); the most common form of degenerative joint disease, is associated with variations in pro-inflammatory growth factor levels, inflammation and hypocellularity resulting from chondrocyte apoptosis. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide endowed with a range of trophic effects in several cell types; including chondrocytes. However; its role in OA has not been studied. To address this issue, we investigated whether PACAP expression is affected in OA cartilage obtained from experimentally-induced OA rat models, and then studied the effects of PACAP in isolated chondrocytes exposed to IL-1β in vitro to mimic the inflammatory milieu of OA cartilage. OA induction was established by histomorphometric and histochemical analyses. Changes in PACAP distribution in cartilage, or its concentration in synovial fluid (SF), were assessed by immunohistochemistry and ELISA. Results showed that PACAP abundance in cartilage tissue and SF was high in healthy controls. OA induction decreased PACAP levels both in affected cartilage and SF. In vitro, PACAP prevented IL-1β-induced chondrocyte apoptosis, as determined by MTT assay; Hoechst staining and western blots of apoptotic-related proteins. These changes were also accompanied by decreased i-NOS and COX-2 levels, suggesting an anti-inflammatory effect. Altogether, these findings support a potential role for PACAP as a chondroprotective agent for the treatment of OA.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy. sgiunta@unict.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Giunta
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy. alecasto@unict.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Castorina
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy. rubinamarzagalli@yahoo.it.
authors.forename: Rubina
authors.initials: R
authors.lastname: Marzagalli
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy. mszychlinska@unict.it.
authors.forename: Marta Anna
authors.initials: MA
authors.lastname: Szychlinska
authors.affiliation: Department of Pediatrics, Clinic for Pediatrics I Medical University of Innsbruck, Anichstr. 35, A-6020 Innsbruck, Austria. karin_pichler@hotmail.com.
authors.forename: Karin
authors.initials: K
authors.lastname: Pichler
authors.affiliation: The D-BOARD European Consortium for Biomarker Discovery, Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK. a.mobasheri@surrey.ac.uk.|Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. a.mobasheri@surrey.ac.uk.|Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), King AbdulAziz University, Jeddah 21589, Saudi Arabia. a.mobasheri@surrey.ac.uk.
authors.forename: Ali
authors.initials: A
authors.lastname: Mobasheri
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Via S. Sofia 87, 95123 Catania, Italy. g.musumeci@unict.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000032:analysis / Q000494:pharmacology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D053583:Interleukin-1beta; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2