Dataset Information

Arterial injury promotes medial chondrogenesis in Sm22 knockout mice.

ABSTRACT:

Aims

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.

Methods and 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 ?-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-?B pathway activation.

Conclusion

These findings suggest that disruption of SM22 alters the actin cytoskeleton and promotes chondrogenic conversion of VSMCs.

SUBMITTER: Shen J

PROVIDER: S-EPMC3058734 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Publications

Arterial injury promotes medial chondrogenesis in Sm22 knockout mice.

Shen Jianbin J Yang Maozhou M Jiang Hong H Ju Donghong D Zheng Jian-Pu JP Xu Zhonghui Z Liao Tang-Dong TD Li Li L

Cardiovascular research 20101222 1

<h4>Aims</h4>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.<h4>Methods and results</h4>Sm22 knockout (Sm22(-/-)) mice developed prominent medial chondrogenesis 2 weeks after carotid denudation as evidenced by the enhanced expre ...[more]

PMID: 21183509

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Project description:Vascular calcification, prevalent in diabetes and chronic kidney disease, contributes to morbidity and mortality. To investigate the effect of receptor activator of NF-kB ligand (RANKL) on vascular calcification in vivo, transgenic mice, where RANKL expression was targeted to vascular smooth muscle cells using the SM22? promoter (SM22?-Rankl ( tg )), were created. Sixteen-month-old male SM22?-Rankl ( tg ) mice had higher body weight and higher serum calcium levels but lower lumbar bone mineral density (BMD) compared with age- and gender-matched wild-type (WT) littermates. BMD of long bones, body fat (percent of weight) of the leg, and serum levels of phosphate and RANKL were not significantly different. No significant differences in these parameters were observed in female mice. Histological analysis did not reveal calcium deposits in the aortic roots of SM22?-Rankl ( tg ) mice. To analyze the osteoblastic differentiation and mineralization potentials of vascular cells, aortic smooth muscle cells (SMCs) were isolated and cultured. Results showed that SM22?-Rankl ( tg ) SMCs had higher baseline alkaline phosphatase (ALP) activity but not baseline matrix calcification. When induced by the PKA agonist forskolin, ALP activity was greater in SM22?-Rankl ( tg ) than in WT SMCs. Real-time RT-qPCR revealed higher baseline expression of ALP and ankylosis genes but lower osteoprotegerin gene in SM22?-Rankl ( tg ) SMCs. Matrix mineralization induced by inorganic phosphate or forskolin was greater in SM22?-Rankl ( tg ) than in WT SMCs. Treatment of these cells with the ALP inhibitor levamisole abolished forskolin-induced matrix mineralization but not inorganic phosphate-induced matrix mineralization. These findings suggest that RANKL overexpression in the vasculature may promote mineralization potential.

Dataset Information

Arterial injury promotes medial chondrogenesis in Sm22 knockout mice.

Aims

Methods and results

Conclusion

Publications

Arterial injury promotes medial chondrogenesis in Sm22 knockout mice.

Similar Datasets

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