title: Transforming growth factor-β1 induces type II collagen and aggrecan expression via activation of extracellular signal-regulated kinase 1/2 and Smad2/3 signaling pathways.
abstract: Transforming growth factor (TGF)‑β regulates the anabolic metabolism of articular cartilage and prevents cartilage degradation. TGF‑β1 influences cellular proliferation, differentiation and the extracellular matrix through activation of the extracellular signal‑regulated kinase (ERK)1/2 and Smad2/3 signaling pathways. However, it has remained to be fully elucidated precisely how the ERK1/2 and Smad2/3 signaling pathways mediate anabolic processes of articular cartilage. The present study investigated how ERK1/2 and Smad2/3 signaling mediate TGF‑β1‑stimulated type II collagen and aggrecan expression in rat chondrocytes. The results confirmed that TGF‑β1 stimulates type II collagen and aggrecan expression in rat chondrocytes, and furthermore, that the ERK1/2 and Smad2/3 signaling pathways were activated by TGF‑β1. Conversely, the TGF‑β receptor I (ALK5) kinase inhibitor SB525334 significantly impaired TGF‑β1‑induced type II collagen and aggrecan expression, coinciding with a reduction of ERK1/2 and Smad3 phosphorylation. In addition, TGF‑β1‑induced type II collagen and aggrecan expression were significantly suppressed by ERK1/2 inhibitor PD98059. Similarly, TGF‑β1‑stimulated type II collagen and aggrecan expression were decreased in the presence of a Smad3 phosphorylation inhibitor SIS3. Therefore, the present study demonstrated that the ERK1/2 and Smad2/3 signaling pathways regulate type II collagen and aggrecan expression in rat chondrocytes.
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, P.R. China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, P.R. China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Tao
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, P.R. China.
authors.forename: Yonzhang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, P.R. China.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, P.R. China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
mesh_terms: D053674:Aggrecans / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D051899:Smad2 Protein / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D051900:Smad3 Protein / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C508504:6,7-dimethyl-2-(2E)-3-(1-methyl-2-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl-prop-2-enoyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride; C521813:6-(2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline; D053674:Aggrecans; D024043:Collagen Type II; D005419:Flavonoids; D007093:Imidazoles; D007546:Isoquinolines; D011725:Pyridines; D011758:Pyrroles; D011810:Quinoxalines; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625843:Tgfbr1 protein, rat; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one