Talk:Musculoskeletal System - Cartilage Development

2010

The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9

J Cell Sci. 2010 Oct 12.

Takigawa Y, Hata K, Muramatsu S, Amano K, Ono K, Wakabayashi M, Matsuda A, Takada K, Nishimura R, Yoneda T.

Abstract Sox9 is an essential transcription factor for chondrogenesis by regulating the expression of chondrogenic genes. However, its regulatory mechanism is not fully understood. To address this, we attempted to identify the transcriptional partners of Sox9 by screening the cDNA library of the chondrogenic cell line ATDC5 using the collagen 2α1 (Col2α1) gene promoter fused to a luciferase reporter gene. One of the positive clones encoded the Znf219 gene. Whole mount in situ hybridization experiments indicated that Znf219 mRNA was specifically expressed in the developing limb buds where Col2α1 and Sox9 were strongly expressed. Znf219 markedly enhanced the transcriptional activity of Sox9 on the Col2a1 gene promoter. In addition, Znf219 is physically associated with Sox9 and is colocalized with Sox9 in the nucleus. We also found that overexpression of Znf219 profoundly increased Sox9-induced mRNA expression of Col2a1, aggrecan and Col11a2. Consistently, knockdown of Znf219 decreased the Sox9-induced mRNA expression of these genes. Furthermore, a dominant-negative mutant Znf219 inhibited Bmp2-induced chondrocyte differentiation. Our results suggest that Znf219 plays an important role in the regulation of chondrocyte differentiation as a transcriptional partner of Sox9.

PMID: 20940257

Expression of cartilage developmental genes in Hoxc8- and Hoxd4-transgenic mice

Kruger C, Kappen C. PLoS One. 2010 Feb 2;5(2):e8978. PMID: 20126390

The control of chondrogenesis

J Cell Biochem. 2006 Jan 1;97(1):33-44.

Goldring MB, Tsuchimochi K, Ijiri K. Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, New England Baptist Bone and Joint Institute and Harvard Medical School, Boston, MA 02115, USA. mgoldrin@bidmc.harvard.edu

Abstract Chondrogenesis is the earliest phase of skeletal development, involving mesenchymal cell recruitment and migration, condensation of progenitors, and chondrocyte differentiation, and maturation and resulting in the formation of cartilage and bone during endochondral ossification. This process is controlled exquisitely by cellular interactions with the surrounding matrix, growth and differentiation factors, and other environmental factors that initiate or suppress cellular signaling pathways and transcription of specific genes in a temporal-spatial manner. Vertebrate limb development is controlled by interacting patterning systems involving prominently the fibroblast growth factor (FGF), bone morphogenetic protein (BMP), and hedgehog pathways. Both positive and negative signaling kinases and transcription factors, such as Sox9 and Runx2, and interactions among them determine whether the differentiated chondrocytes remain within cartilage elements in articular joints or undergo hypertrophic maturation prior to ossification. The latter process requires extracellular matrix remodeling and vascularization controlled by mechanisms that are not understood completely. Recent work has revealed novel roles for mediators such as GADD45beta, transcription factors of the Dlx, bHLH, leucine zipper, and AP-1 families, and the Wnt/beta-catenin pathway that interact at different stages during chondrogenesis. (c) 2005 Wiley-Liss, Inc.

PMID: 16215986

The life cycle of chondrocytes in the developing skeleton

Arthritis Res. 2002;4(2):94-106. Epub 2001 Nov 8.

Shum L, Nuckolls G. Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH, 6 Center Drive, Bldg 6 Rm 324, Bethesda, MD 20892-2745, USA.

Abstract Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joint formation. Extracellular growth and differentiation factors including bone morphogenetic proteins, fibroblast growth factors, parathyroid hormone-related peptide, extracellular matrix components, and members of the hedgehog and Wnt families provide important signals for the regulation of cell proliferation, differentiation and apoptosis. Transduction of these signals within the developing mesenchymal cells and chondrocytes results in changes in gene expression mediated by transcription factors including Smads, Msx2, Sox9, signal transducer and activator of transcription (STAT), and core-binding factor alpha 1. Further investigation of the interactions of these signaling pathways will contribute to an understanding of cartilage growth and development, and will allow for the development of strategies for the early detection, prevention and treatment of diseases and disorders affecting the skeleton.

PMID: 11879545 http://www.ncbi.nlm.nih.gov/pubmed/11879545

http://arthritis-research.com/content/4/2/94