Constitutive L-Sox5 overexpression delays differentiation of ATDC5 cells into chondrocytes and correlates with reduced expression of differentiation markers
参考文献:1. Mackie EJ, Ahmed YA, Tatarczuch L, Chen KS, Mirams M (2008) Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol 40:46鈥?2 CrossRef 2. Lefebvre V, Smits P (2005) Transcriptional control of chondrocyte fate and differentiation. Birth Defects Res C Embryo Today 75:200鈥?12 CrossRef 3. Akiyama H, Lefebvre V (2011) Unraveling the transcriptional regulatory machinery in chondrogenesis. J Bone Miner Metab 29:390鈥?95 CrossRef 4. Lefebvre V, Li P, de Crombrugghe B (1998) A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene. EMBO J 17:5718鈥?733 CrossRef 5. Saito T, Ikeda T, Nakamura K, Chung UI, Kawaguchi H (2007) S100A1 and S100B, transcriptional targets of SOX trio, inhibit terminal differentiation of chondrocytes. EMBO Rep 8:504鈥?09 CrossRef 6. Atsumi T, Miwa Y, Kimata K, Ikawa Y (1990) A chondrogenic cell line derived from a differentiating culture of AT805 teratocarcinoma cells. Cell Differ Dev 30:109鈥?16 CrossRef 7. Yao Y, Wang Y (2013) ATDC5: an excellent in vitro model cell line for skeletal development. J Cell Biochem 114:1223鈥?229 CrossRef 8. Cancedda R, Descalzi Cancedda F, Castagnola P (1995) Chondrocyte differentiation. Int Rev Cytol 159:265鈥?58 CrossRef 9. Murdoch AD, Grady LM, Ablett MP, Katopodi T, Meadows RS, Hardingham TE (2007) Chondrogenic differentiation of human bone marrow stem cells in transwell cultures: generation of scaffold-free cartilage. Stem Cells 25:2786鈥?796 CrossRef 10. Hattori T, Kishino T, Stephen S, Eberspaecher H, Maki S, Takigawa M et al (2013) E6-AP/UBE3A protein acts as a ubiquitin ligase toward SOX9 protein. J Biol Chem 288:35138鈥?5148 CrossRef 11. An CI, Ganio E, Hagiwara N (2013) Trip12, a HECT domain E3 ubiquitin ligase, targets Sox6 for proteasomal degradation and affects fiber type-specific gene expression in muscle cells. Skelet Muscle 3:11 CrossRef 12. Hall BK, Miyake T (1995) Divide, accumulate, differentiate: cell condensation in skeletal development revisited. Int J Dev Biol 39:881鈥?93 13. Shukunami C, Ishizeki K, Atsumi T, Ohta Y, Suzuki F, Hiraki Y (1997) Cellular hypertrophy and calcification of embryonal carcinoma-derived chondrogenic cell line ATDC5 in vitro. J Bone Miner Res 12:1174鈥?188 CrossRef 14. Chou CH, Lee CH, Lu LS, Song IW, Chuang HP, Kuo SY et al (2013) Direct assessment of articular cartilage and underlying subchondral bone reveals a progressive gene expression change in human osteoarthritic knees. Osteoarthritis Cartilage 21:450鈥?61 CrossRef 15. Iwamoto M, Kitagaki J, Tamamura Y, Gentili C, Koyama E, Enomoto H et al (2003) Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP). Osteoarthritis Cartilage 11:6鈥?5 CrossRef 16. Smits P, Li P, Mandel J, Zhang Z, Deng JM, Behringer RR et al (2001) The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev Cell 1:277鈥?90 CrossRef 17. Nagy A, Kenesi E, Rentsendorj O, Molnar A, Szenasi T, Sinko I et al (2011) Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1 promoter: L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by Sox9. Mol Cell Biol 31:686鈥?99 CrossRef 18. Li H, Haudenschild DR, Posey KL, Hecht JT, Di Cesare PE, Yik JH (2011) Comparative analysis with collagen type II distinguishes cartilage oligomeric matrix protein as a primary TGFbeta-responsive gene. Osteoarthritis Cartilage 19:1246鈥?253 CrossRef
刊物类别:Biomedical and Life Sciences
刊物主题:Life Sciences Biochemistry Medical Biochemistry Oncology Cardiology
出版者:Springer Netherlands
ISSN:1573-4919
文摘
L-Sox5 is a member of sex-determining region Y-type high mobility group box (SOX) family of transcription factors. We assessed the effects of retroviral overexpression of L-Sox5 on chondrocyte differentiation using the clonal murine cell line ATDC5. We observed a temporal-restricted expression pattern of L-Sox5 in insulin-induced ATDC5 cells differentiating toward chondrocyte lineage. The protein expression levels of L-Sox5 showed a drastic decrease in contrast to unaltered mRNA levels during differentiation. L-Sox5 delayed the differentiation of ATDC5 cells as evidenced by Alcian blue staining for proteoglycan synthesis. The mRNA levels of chondrocyte and hypertrophic/osteoarthritic markers were markedly decreased or delayed in L-Sox5 overexpressing cells. L-Sox5 abrogated the promoter activity of Runx2. These results suggest that L-Sox5 protein expression may diminish along with the progress of chondrogenic differentiation. L-Sox5 may act as a negative regulator if expressed aberrantly at least in part by regulating the critical fate of chondrogenesis.