Overexpression of SOX9 in mouse embryonic stem cells directs the immediate chondrogenic commitment

Kim, Jaehwan; Do, Hyun-Jin; Yang, Hyun Ok; Oh, Jonghyun; Choi, Seong–Jun; Kim, Dong-Ku; Cha, Kwang-Yul; Chung, Hyung-Min

doi:10.1038/emm.2005.35

Cited by 26 publications

(19 citation statements)

References 41 publications

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“…12 The expression of sox9 in primitive mesenchymal cells induced chondrocytic phenotype: for example, the expression of cartilage-specific matrix molecules such as type II collagen and aggrecan. 19,20 In these cases, the expression of sox9 was more diffuse in the nuclei of metaplastic cells than in carcinomatous cells. S-100 protein expression in matrix-producing carcinoma, especially in metaplastic cells, is well known 2 and is frequently seen in chondrocytes and chondrocytic tumors.…”

Section: Discussionmentioning

confidence: 86%

Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules

et al. 2008

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Matrix-producing carcinoma of the breast is a well-established entity in the group of metaplastic carcinoma, which is histologically characterized by myxochondroid matrix formation and is extremely rare. We describe here four additional cases of matrix-producing carcinoma of the breast. All cases of matrix-producing carcinoma show nest-like, sheet-like, and cord-like growth of tumor cells with cellular atypia, in addition to scattered cancer cells within myxoid or myxohyalinous stroma. Three of four cases showed an acellular or oligocellular matrix-rich zone in the center of the tumor. Immunohistochemically, cancer cells of all cases were positive for cytokeratins and epithelial membrane antigens and partially positive for sox9 and p63. Aggrecan and type II collagen, which are cartilage-specific matrix molecules, were deposited in the stroma of all cases. Type I and type IV collagens were also deposited on the stroma of all cases. These findings suggest that, although cancer cells of matrix-producing carcinoma of the breast are epithelial, they transdifferentiate to chondrocyte-like cells and produce cartilage-specific matrix molecules, which are useful markers for diagnosing matrix-producing carcinoma. Modern Pathology (2008Pathology ( ) 21, 1282Pathology ( -1292 doi:10.1038/modpathol.2008 published online 11 July 2008 Keywords: aggrecan; collagens; matrix-producing carcinoma; breast; immunohistochemistry; electron-microscopy Matrix-producing carcinoma of the breast is an extremely rare and specialized variant of metaplastic carcinoma of the breast, which is a well-established entity; 1,2 because of its rarity, the features of its stroma have remained unclear.Aggrecan is a cartilage-specific major proteoglycan. 3 This macromolecule deposits in the hypertrophic zones of growth plate cartilage, 4 although it was reported to deposit in the salivary pleomorphic adenoma, which frequently showed mesenchyme-like elements, including myxoid and chondroid tissues. 5,6 Type II collagen, which is a cartilage-specific major collagen, and chondromodulin-I (ChM-I), which is cartilage-specific noncollagenous matrix protein, 4,7,8 are deposited in the normal cartilaginous matrix. These molecules can be useful markers of cartilaginous differentiation. As sox9 is a transcription factor, the expression of which induces cartilaginous differentiation, 9-11 this molecule is also a useful marker of chondroid differentiation in normal and neoplastic tissues. [9][10][11][12] We investigated the deposition of matrix molecules in matrix-producing carcinoma of the breast, histochemically and immunohistochemically.

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Section: Discussionmentioning

confidence: 86%

Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules

et al. 2008

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“…The Sox9 gene has been shown to be expressed in all chondroprogenitors and plays an essential role in chondrogenesis. The directed overexpression of Sox9 in mouse embryonic stem cells can drive chondrogenic commitment [27]. Fibroblast-like chondrocytes can contribute to the formation of scar tissue [28], producing type I collagen, and not the type II collagen typical for healthy cartilage.…”

Section: Discussionmentioning

confidence: 99%

Laser Capture Microdissection-Microarray Analysis of Focal Segmental Glomerulosclerosis Glomeruli

Bennett

Czech

Arend

et al. 2007

Nephron Exp Nephrol

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Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease. In this report we used laser capture microdissection to purify diseased glomeruli, and microarrays to provide universal gene expression profiles. The results provide a deeper understanding of the molecular mechanisms of the disease process and suggest novel therapeutic strategies. Consistent with earlier studies, molecular markers of the differentiated podocyte, including WT1, nephrin, and VEGF, were dramatically downregulated in the diseased glomerulus. We also observed multiple changes consistent with increased TGF-β signaling, including elevated expression of TGF-β₂, TGF-β₃, SMAD2, TGF-β₁ receptor, and thrombospondin. In addition, there was relatively low level expression of Csf1r, a marker of macrophages, but elevated expression of the chemokines CXCL1, CXCL2, CCL3, and CXCL14. We also observed strongly upregulated expression of Sox9, a transcription factor that can drive a genetic program of chondrogenesis and fibrosis. Further, the gene with the greatest fold increase in expression in the diseased glomerulus was osteopontin, which has been previously strongly implicated in kidney fibrosis in the unilateral ureteral obstruction mouse model. These results confirm old findings, and indicate the involvement of new genetic pathways in the cause and progression of FSGS.

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“…The differentiation of chondrocyte of Meckel's cartilage may be mainly regulated by genetic determinants but environmental influences may also concomitantly react (Chung and Nishimura, 1999;Kim et al, 2005). The developing incisor may be an environmentally affecting factor.…”

Section: Discussionmentioning

confidence: 99%

gp130 is important for the normal morphogenesis of Meckel's cartilage and subsequent mandibular development

Choi

Kim²,

Park³

et al. 2007

Exp Mol Med

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gp130-mediated signaling is involved in both chondrogenesis and osteogenesis, but its direct role in the formation of embryonic Meckel's cartilage and associated mandibular development has not yet been elucidated. In this study, we examined the influence of gp130 ablation on the developing mandibular Meckel's cartilage by evaluating the morphological and histological changes as well as the gene expression patterns in developing embryonic gp130-/-mice. The ablation of the gp130 gene showed no change in region-specific collagen mRNA expression except for a slight delay in its expression but caused shortened embryonic Meckel's cartilage, delayed hypertrophic chondrocyte maturation and subsequent bony replacement with characteristic bending of the intramandibular Meckel's cartilage. The bending of Meckel's cartilage led to a narrow mandibular arch at the rostral area with poor cortical plate formation. These findings indicate that gp130-mediated signaling is important for the normal morphogenesis of Meckel's cartilage and subsequent mandibular development.

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Overexpression of SOX9 in mouse embryonic stem cells directs the immediate chondrogenic commitment

Cited by 26 publications

References 41 publications

Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules

Cartilaginous features in matrix-producing carcinoma of the breast: four cases report with histochemical and immunohistochemical analysis of matrix molecules

Laser Capture Microdissection-Microarray Analysis of Focal Segmental Glomerulosclerosis Glomeruli

gp130 is important for the normal morphogenesis of Meckel's cartilage and subsequent mandibular development

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