Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2
Copyright policy )Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2
SignificanceHere we demonstrate that Hes1, an important target of Notch signaling, modulated pathogenesis of osteoarthritis by usingCol2a1-CreERT;Hes1fl/flmice.Adamts5andMmp13, catabolic enzymes that break down cartilage matrix, were induced by Hes1. Additionally, microarray analysis and ChIP-seq revealed novel Hes1 target genes, includingIl6andIl1rl1, coding a receptor for IL-33. CaMK2δ was activated during osteoarthritis development. CaMK2δ formed a protein complex with Hes1, and switched it from a transcriptional repressor to a transcriptional activator to induce cartilage catabolic factors.
Homeodomain Proteins, Transcription, Genetic, Mice, Transgenic, Mice, Inbred C57BL, Mice, HEK293 Cells, Gene Expression Regulation, Osteoarthritis, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Transcription Factor HES-1, Calcium-Calmodulin-Dependent Protein Kinase Type 2, HeLa Cells
Homeodomain Proteins, Transcription, Genetic, Mice, Transgenic, Mice, Inbred C57BL, Mice, HEK293 Cells, Gene Expression Regulation, Osteoarthritis, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Transcription Factor HES-1, Calcium-Calmodulin-Dependent Protein Kinase Type 2, HeLa Cells
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