title: JNK/ERK-AP-1/Runx2 induction "paves the way" to cartilage load-ignited chondroblastic differentiation.
abstract: Chondro-osteogenesis and subsequently skeletal morphology are greatly influenced by mechanical loads. The exact mechanism(s) by which mechanical stimuli are transduced in chondrocytes remains obscure and appears to be equally complex with similar signal transducing systems. Here we investigated whether and to what extent the MAPK (JNK/ERK)-AP-1/Runx2 signaling pathways are engaged in this phenomenon, and assessed their involvement in the functional biology of articular cartilage. For this purpose, 14-day-old female Wistar rats were divided into 2 groups: the first group was fed hard diet (simulating physiologic temporomandibular joint (TMJ) loading), while the second group was fed soft diet (reduced TMJ loading). On day 21 (experiment initiation day - weaning day), biopsies from condyles of both groups were obtained after 6, 12 and 48 h of functional TMJ loading. Immunohistochemical methodology was employed to evaluate the expression levels of pc-Jun, c-Fos, JNK2, p-JNK, p-ERK and Runx2 due to alteration in functional load. Our data demsonstrate that the protein levels of all the aforementioned molecules were markedly increased in animals fed with the hard diet, throughout the experimental procedure. These results indicate that functional cartilage loading induces the AP-1 and Runx2 transcription factors through the JNK and ERK MAPK cascades. In as much as the above signaling mediators/effectors are considered to be crucial in the differentiation/maturation process of cartilage tissue, we pose that functional mechanical loading of condylar cartilage serves to "fine tune" chondroblastic differentiation/maturation.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Patras, Greece.
authors.forename: Dionysios J
authors.initials: DJ
authors.lastname: Papachristou
authors.forename: Pertti
authors.initials: P
authors.lastname: Pirttiniemi
authors.forename: Tuomo
authors.initials: T
authors.lastname: Kantomaa
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
authors.forename: Efthimia K
authors.initials: EK
authors.lastname: Basdra
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D004032:Diet; D004790:Enzyme Induction; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005260:Female; D016762:Genes, fos; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000502:physiology*; D048056:Mitogen-Activated Protein Kinase 9 / Q000096:biosynthesis; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013704:Temporomandibular Joint / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000096:biosynthesis
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493717:Runx2 protein, rat; D018808:Transcription Factor AP-1; D048056:Mitogen-Activated Protein Kinase 9; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases