Akt signaling regulates actin organization via modulation of MMP‐2 activity during chondrogenesis of chick wing limb bud mesenchymal cells

Journal of Cellular Biochemistry - Tập 102 Số 1 - Trang 252-261 - 2007
Eun‐Jung Jin1, Kwang Sook Park1, Ok‐Sun Bang2, Shin‐Sung Kang3,1
1Department of Biology, College of Natural Sciences (BK21), Kyungpook National University, Daegu 702-701, Korea
2Department of Medical Research, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea
3Daegu Center, Korea Basic Science Institute, Daegu 702-701, Korea

Tóm tắt

AbstractEndochondral ossification is initiated by the differentiation of mesenchymal precursor cells to chondrocytes. This process is characterized by a strong interdependence of cell shape and cytoskeletal organization accompanying the onset of chondrogenic gene expression, but the molecular mechanisms mediating these interactions are not known. In this study, we hypothesized that the activation of matrix metalloproteinase (MMP)‐2 would be involved in the reorganization of the actin cytoskeleton and that this would require an Akt‐dependent signaling pathway in chick wing bud mesenchymal cells. The pharmacological inhibition of Akt signaling resulted in decreased glycosaminoglycan synthesis and reduced the level of active MMP‐2, leading to suppressed cortical actin organization which is characteristic of differentiated chondrocytes. In addition, the exposure of cells to bafilomycin A1 reversed these chondro‐inhibitory effects induced by inhibition of Akt signaling. In conclusion, our data indicate that Akt signaling is involved in the activation of MMP‐2 and that this Akt‐induced activation of MMP‐2 is responsible for reorganization of the actin cytoskeleton into a cortical pattern with parallel rounding of chondrogenic competent cells. J. Cell. Biochem. 102: 252–261, 2007. © 2007 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1242/jcs.100.2.249

Davies MA, 1999, Regulation of Akt/PKB activity, cellular growth, and apoptosis in prostate carcinoma cells by MMAC/PTEN, Cancer Res, 59, 2551

10.1053/joca.1999.0306

10.1016/S0955-0674(98)80149-X

10.1046/j.1365-2842.1997.00458.x

10.1016/S0092-8674(00)81883-8

10.1074/jbc.M011265200

Hayakawa J, 2000, Inhibition of BAD phosphorylation either at serine 112 via extracellular signal‐regulated protein kinase cascade or at serine 136 via Akt cascade sensitizes human ovarian cancer cells to cisplatin, Cancer Res, 60, 5988

10.1126/science.275.5300.628

10.1023/A:1004095207330

10.1074/jbc.M101463200

Jin EJ, 2006, BMP‐2‐enhanced chondrogenesis involves p38 MAPK‐mediated down‐regulation of Wnt‐7a pathway, Mol Cells, 22, 353, 10.1016/S1016-8478(23)17431-0

10.1016/S1534-5807(02)00157-0

10.1096/fj.01-0198com

10.1074/jbc.M304887200

10.1128/MCB.17.1.338

10.1038/sj.onc.1204799

10.3171/jns.2001.95.3.0480

10.1177/002215540004801002

10.1242/jcs.114.16.2903

10.1189/jlb.0306160

10.1038/sj.cdd.4401106

10.1006/bbrc.2000.2987

10.1007/BF01953199

10.1042/bj20030170

10.1158/0008-5472.CAN-04-3399

10.1186/ar2034

10.1016/j.ygyno.2004.03.039

10.1074/jbc.275.8.5613

10.1016/j.matbio.2005.06.009

Park MJ, 2002, PTEN suppresses hyaluronic acid‐induced matrix metalloproteinase‐9 expression in U87MG glioblastoma cells through focal adhesion kinase dephosphorylation, Cancer Res, 626318

10.1016/j.joms.2005.05.319

10.1186/ar148

10.1053/joca.2001.0482

10.1016/j.bbrc.2006.07.002

Soder S, 2006, MMP‐9/gelatinase B is a gene product of human adult articular chondrocytes and increased in osteoarthritic cartilage, Clin Exp Rheumatol, 24, 302

10.1016/0045-6039(84)90046-0

10.1074/jbc.M414275200

10.1073/pnas.211430998

von der Mark K, 1977, The role of three genetically distinct collagen types in endochondral ossification and calcification of cartilage, J Bone Joint Surg Br, 59, 458, 10.1302/0301-620X.59B4.72756

10.1074/jbc.275.16.12353

10.1078/0171-9335-00134

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Thông tin xuất bản

Journal of Cellular Biochemistry

Tập 102 Số 1

252-261

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