title: A candidate enhancer element responsible for high-level expression of the aggrecan gene in chondrocytes.
abstract: Aggrecan is the most abundant proteoglycan in cartilage. It contains a lot of negatively charged glycosaminoglycan chains along the core protein, providing a large osmotic swelling pressure within the cartilage. Therefore, the biomechanical properties of cartilage, such as its compressive load-bearing capacity, are highly dependent on the presence of abundant aggrecan in the cartilage matrix. To elucidate the transcriptional mechanism that leads to abundant expression of aggrecan by chondrocytes, we screened for enhancer elements in 130 kb of the aggrecan gene, Agc1, using a reporter assay system that we previously developed. The system is based on co-transfection of candidate enhancer elements and reporter constructs into Swarm rat chondrosarcoma chondrocytes that retain a high level of aggrecan expression. We found an element that might be involved in high-level expression of Agc1 gene in chondrocytes in vivo. The element is located 30 kb upstream of the Agc1 transcription start site.
authors.affiliation: Tissue Regeneration; Periodontology, Department of Bio-Matrix, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; and Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, JapanTissue Regeneration; Periodontology, Department of Bio-Matrix, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; and Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Tissue Regeneration; Periodontology, Department of Bio-Matrix, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; and Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ito
authors.affiliation: Tissue Regeneration; Periodontology, Department of Bio-Matrix, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; and Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Tissue Regeneration; Periodontology, Department of Bio-Matrix, Tokyo Medical and Dental University, Tokyo 113-8549, Japan; and Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan t.shinomura.trg@tmd.ac.jp.
authors.forename: Tamayuki
authors.initials: T
authors.lastname: Shinomura
mesh_terms: D053674:Aggrecans / Q000235:genetics*; D000818:Animals; D019902:Chondrocytes / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: C508321:Acan protein, rat; D053674:Aggrecans
keywords: Aggrecan; cartilage; extracellular matrix; transcriptional enhancer; type II collagen