title: Arterial injury promotes medial chondrogenesis in Sm22 knockout mice.
abstract: OBJECTIVE
  Expression of SM22 (also known as SM22alpha and transgelin), a vascular smooth muscle cells (VSMCs) marker, is down-regulated in arterial diseases involving medial osteochondrogenesis. We investigated the effect of SM22 deficiency in a mouse artery injury model to determine the role of SM22 in arterial chondrogenesis.
  
  
  RESULTS
  Sm22 knockout (Sm22(-/-)) mice developed prominent medial chondrogenesis 2 weeks after carotid denudation as evidenced by the enhanced expression of chondrogenic markers including type II collagen, aggrecan, osteopontin, bone morphogenetic protein 2, and SRY-box containing gene 9 (SOX9). This was concomitant with suppression of VSMC key transcription factor myocardin and of VSMC markers such as SM α-actin and myosin heavy chain. The conversion tendency from myogenesis to chondrogenesis was also observed in primary Sm22(-/-) VSMCs and in a VSMC line after Sm22 knockdown: SM22 deficiency altered VSMC morphology with compromised stress fibre formation and increased actin dynamics. Meanwhile, the expression level of Sox9 mRNA was up-regulated while the mRNA levels of myocardin and VSMC markers were down-regulated, indicating a pro-chondrogenic transcriptional switch in SM22-deficient VSMCs. Furthermore, the increased expression of SOX9 was mediated by enhanced reactive oxygen species production and nuclear factor-κB pathway activation.
  
  
  CONCLUSIONS
  These findings suggest that disruption of SM22 alters the actin cytoskeleton and promotes chondrogenic conversion of VSMCs.
authors.affiliation: Department of Internal Medicine, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Shen
authors.forename: Maozhou
authors.initials: M
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Donghong
authors.initials: D
authors.lastname: Ju
authors.forename: Jian-Pu
authors.initials: JP
authors.lastname: Zheng
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Xu
authors.forename: Tang-Dong
authors.initials: TD
authors.lastname: Liao
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054338:Cell Transdifferentiation / Q000235:genetics; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology*; D020219:Chondrogenesis / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005838:Genotype; D008297:Male; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics; D024510:Muscle Development; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010641:Phenotype; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D017540:Tunica Media / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C058992:Tagln protein, mouse; D014157:Transcription Factors