Akt signaling regulates actin organization via modulation of MMP‐2 activity during chondrogenesis of chick wing limb bud mesenchymal cells
Tóm tắt
Endochondral 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.
Từ khóa
Tài liệu tham khảo
Davies MA, 1999, Regulation of Akt/PKB activity, cellular growth, and apoptosis in prostate carcinoma cells by MMAC/PTEN, Cancer Res, 59, 2551
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
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
Park MJ, 2002, PTEN suppresses hyaluronic acid‐induced matrix metalloproteinase‐9 expression in U87MG glioblastoma cells through focal adhesion kinase dephosphorylation, Cancer Res, 626318
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
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