title: PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway.
abstract: This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2) in chondrogenic differentiation of mesenchymal stem cells (MSCs). MSCs were isolated from femurs and tibias of Sprague-Dawley rats, weighing 300-400 g (5 females and 5 males). Overexpression and knockdown of PDK2 were transfected into MSCs and then cell viability, adhesion and migration were assessed. Additionally, the roles of aberrant PDK2 in chondrogenesis markers SRY-related high mobility group-box 6 (Sox6), type ΙΙ procollagen gene (COL2A1), cartilage oligomeric matrix protein (COMP), aggrecan (AGC1), type ΙX procollagen gene (COL9A2) and collagen type 1 alpha 1 (COL1A1) were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The expressions of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and extracellular regulated protein kinase (ERK) were measured. Overexpressing PDK2 promoted cell viability, adhesion and inhibited cell migration in MSCs (all P<0.05). qRT-PCR assay showed a potent increase in the mRNA expressions of all chondrogenesis markers in response to overexpressing PDK2 (P<0.01 or P<0.05). PDK2 overexpression also induced a significant accumulation in mRNA and protein expressions of JNK, p38MAPK and ERK in MSCs compared to the control (P<0.01 or P<0.05). Meanwhile, silencing PDK2 exerted the opposite effects on MSCs. This study shows a preliminary positive role and potential mechanisms of PDK2 in chondrogenic differentiation of MSCs. It lays the theoretical groundwork for uncovering the functions of PDK2 and provides a promising basis for repairing cartilage lesions in osteoarthritis.
authors.affiliation: Second Department of Orthopedics, Baodi Clinical College, Tianjin Medical University, Tianjin, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Second Department of Orthopedics, The First People's Hospital of Yibin, Yibin, China.
authors.forename: X B
authors.initials: XB
authors.lastname: Shan
authors.affiliation: First Department of Orthopedics, 4th (Xing Yuan) Hospital of Yulin, Yulin, China.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Qiao
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D020219:Chondrogenesis / Q000502:physiology*; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017207:Rats, Sprague-Dawley; D055757:SOXE Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: C000716129:Col1a1 protein, rat; D000090602:Collagen Type I, alpha 1 Chain; C000631436:Pdk2 protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D055757:SOXE Transcription Factors; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases