title: p38 MAPK mediated in compressive stress-induced chondrogenesis of rat bone marrow MSCs in 3D alginate scaffolds.
abstract: Mesenchymal stem cells (MSCs) are well known to have the capability to form bone and cartilage, and chondrogenesis derived from MSCs is reported to be affected by mechanical stimuli. This research was aimed to study the effects of cyclic compressive stress on the chondrogenic differentiation of rat bone marrow-derived MSCs (BMSCs) which were encapsulated in alginate scaffolds and cultured with or without chondrogenic medium, and to investigate the role of p38 MAPK phospho-relay cascade in this process. The results show that the gene expression of chondrocyte-specific markers of Col2alpha1, aggrecan, Sox9, Runx2, and Ihh was upregulated by dynamic compressive stress introduced at the 8th day of chondrogenic differentiation in vitro. The p38 MAPK was activated by chondrogenic cytokines in a slow and lagged way, but activated by cyclic compressive stimulation in a rapid and transient manner. And inhibition of p38 activity with SB203580 suppressed gene expression of chondrocyte-specific genes stimulated by chondrogenic medium and (or) cyclic compressive stress. These findings suggest that p38 MAPK signal acts as an essential mediator in the mechano-biochemical transduction and subsequent transcriptional regulation in the process of chondrogenesis.
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Zhao
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Yurong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D053674:Aggrecans / Q000235:genetics; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D020723:Glucuronic Acid / Q000737:chemistry; D053823:Hedgehog Proteins / Q000235:genetics; D006603:Hexuronic Acids / Q000737:chemistry; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011312:Pressure; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055758:SOX9 Transcription Factor / Q000235:genetics; D013314:Stress, Mechanical; D054457:Tissue Scaffolds; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D053674:Aggrecans; D000464:Alginates; C511513:COL2A1 protein, rat; D024043:Collagen Type II; D050659:Core Binding Factor Alpha 1 Subunit; D016207:Cytokines; D053823:Hedgehog Proteins; D006603:Hexuronic Acids; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C493717:Runx2 protein, rat; D055758:SOX9 Transcription Factor; D020723:Glucuronic Acid; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580