title: Connective tissue growth factor induces osteogenic differentiation of vascular smooth muscle cells through ERK signaling.
abstract: Connective tissue growth factor (CTGF) plays an important role in the pathogenesis of atherosclerosis by promoting vascular smooth muscle cell (VSMC) growth, migration, apoptosis, adhesion and the secretion of matrix components. The osteogenic differentiation of VSMCs is essential in the development of vascular calcification. However, the role of CTGF in the transdifferentiation and calcification of VSMCs is unclear. In the present study, we examined whether CTGF stimulates VSMC transdifferentiation. Primary VSMCs were obtained from mouse thoracic aortas by enzymatic digestion and identified by immunostaining for smooth muscle specific α-actin antibody (α-SMA). VSMC calcification was induced by the addition of CTGF to the osteogenic mediaum containing 5-10% FBS in the presence of 0.25 mM ascorbic acid and 10 mM β-glycerophosphate for 14 days. Calcified cells were determined by Alizarin Red S staining. Our results revealed that CTGF induced the expression of several bone markers, including alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG) and core-binding factor subunit α1 (Cbfα1)/runt-related transcription factor 2 (Runx2), as well as calcification. However, the inhibition of extracellular signal-regulated kinase (ERK) activity using the ERK-specific inhibitor, PD98059, blocked the induction of these proteins and VSMC calcification. Based on these data, we conclude that CTGF stimulates the transdifferentiation of VSMCs into osteoblasts and that the ERK signaling pathway appears to play a critical role in this process.
authors.affiliation: Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Han
authors.initials: H
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Houde
authors.initials: H
authors.lastname: Zhou
authors.forename: Eryuan
authors.initials: E
authors.lastname: Liao
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Peng
mesh_terms: D000818:Animals; D015415:Biomarkers; D002113:Calcification, Physiologic / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D055513:Connective Tissue Growth Factor / Q000494:pharmacology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology* / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D055513:Connective Tissue Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases