Retinoic acid regulates programmed cell death through BMP signalling

Rodríguez-León, Joaquín; Merino, Ramón; Macias, D.; Gañán, Yolanda; Santesteban, Elena; Hurlé, Juan M.

doi:10.1038/10098

Cited by 92 publications

(65 citation statements)

References 15 publications

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“…Loss of normal BMP2 expression occurs in prostate and breast cancers and in the microadenomas of familial adenomatous polyposis patients (Harris et al, 1994;Hardwick et al, 2004;Horvath et al, 2004). We and others have shown that recombinant BMP2 can inhibit cell proliferation and induce apoptosis in diverse cell types including cancer cells (e.g., Rogers et al, 1992;Graham et al, 1994;Glozak and Rogers, 1996;Coucouvanis and Martin, 1999;Rodriguez-Leon et al, 1999;Kawamura et al, 2000;Hallahan et al, 2003;Zhang et al, 2003;Hardwick et al, 2004). Thus, normal BMP2 protein levels may suppress tumors in some tissues and altering BMP2 expression may promote the transition from normality to malignancy.…”

Section: Introductionmentioning

confidence: 88%

Modulation of Bone Morphogenetic Protein (BMP) 2 gene expression by Sp1 transcription factors

Rogers

2007

Gene

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Changes in Bone Morphogenetic Protein (BMP) 2 gene expression and activity have been linked to many pathological conditions including cancer, osteoarthritis, and birth defects. BMP2 gene polymorphisms have been linked to osteoporosis and osteoarthritis. Sp1 and related proteins are widely expressed regulators of gene expression whose transcription activating abilities vary in different cells and on different genes. We present data indicating that the ratio of Sp1 and Sp3 isoforms varies in cells that express or do not express BMP2. Furthermore, the orientation of Sp1 sites conserved between four orders of mammals influences BMP2 expression. Together our data indicate that the stoichiometry and orientation of Sp1 and Sp3 complexes on the BMP2 promoter influence BMP2 expression.

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Section: Introductionmentioning

confidence: 88%

Modulation of Bone Morphogenetic Protein (BMP) 2 gene expression by Sp1 transcription factors

Rogers

2007

Gene

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“…34,44 Second, retinoic acid regulates interdigital apoptosis by activating BMP expression and activities. 81 Third, retinoic acid enhances chondrogenesis mediated by BMP-dependent and BMP-independent pathways. 81,111 Therefore, the regulation of chondrogenesis and apoptosis by BMP may rely on the ability of retinoic acid to divert BMP signaling to one pathway as opposed to another, or it may rely on the regulation by retinoic acid on distinct cofactors of BMP signaling for different pathways.…”

Section: Anterior-posterior Patterningmentioning

confidence: 98%

Biology of Developmental and Regenerative Skeletogenesis

Tuan

2004

Clinical Orthopaedics &Amp; Related Research

104

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Embryonic skeletal development involves the recruitment, commitment, differentiation, and maturation of mesenchymal cells into those in the skeletal tissue lineage, specifically cartilage and bone along the intramembranous and endochondral ossification pathways. The exquisite control of skeletal development is regulated at the level of gene transcription, cellular signaling, cell-cell and cell-matrix interactions, as well as systemic modulation. Mediators include transcription factors, growth factors, cytokines, metabolites, hormones, and environmentally derived influences. Understanding the mechanisms underlying developmental skeletogenesis is crucial to harnessing the inherent regenerative potential of skeletal tissues for wound healing and repair, as well as for functional skeletal tissue engineering. In this review, a number of key issues are discussed concerning the current and future challenges of the scientific investigation of developmental skeletogenesis in the embryo, specifically limb cartilage development, and how these challenges relate to regenerative or reparative skeletogenesis in the adult. Specifically, a more complete understanding the biology of skeletogenic progenitor cells and the cellular and molecular mechanisms governing tissue patterning and morphogenesis should greatly facilitate the development of regenerative approaches to cartilage repair.The embryonic limb is one of the most studied developmental model systems. Many fundamental paradigms of developmental biology, including the field concept (ie, limb field), progenitor cells (ie, progress zone cells), positional information, polarity (dorsal/ventral, proximal/distal, and anterior/posterior), epithelial-mesenchymal interactions, diffusible morphogen gradients, and many others either originate from or have been amplified through their association with the biology of limb development. The fact that the skeletal primordium represents the core of the developing limb underscores the importance of the skeletal component of the early limb.The limbs develop from paired primordial buds that appear on the lateral surface of the embryo at specific levels, referred to as limb fields, along its anteriorposterior body axis (Fig 1). At the early stages of limb development, the buds exhibit a paddle shape consisting of undifferentiated mesenchymal cells derived from the lateral plate and somitic mesoderm, covered by ectoderm. The limb cartilage elements form temporally in a proximal to distal sequence, but are initially contiguous. 84 Through the gradual recruitment of cells, the primary condensation of the stylopod (humerus/femur) forms first, the zeugopod (radius-ulna/tibia-fibula) forms second, and the autopod (carpals/tarsals and phalanges) forms last. There is considerable mixing of cells along the proximal-distal axis within each future segment, but not between segments. 28 Positional information is determined in part by the expression of Hox genes. The first part of the limb, in which a subset of Hoxa and Hoxd genes are activated, is the post...

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“…FGFs inhibit chondrogenesis but expand the amount of Sox 9 positive skeletal progenitors and its overexpression in the limb results in the formation of extra cartilages, including extra-digits (Montero et al, 2001; Norrie et al, 2014), or extra-phalanxes (Sanz-Ezquerro and Tickle, 2003b). RA is a potent inhibitor of Sox9 gene expression (Weston et al, 2002) and RA inhibition in the autopod causes the formation of extra digits (Rodriguez-Leon et al, 1999). Hence, the pattern of Sox9 gene expression may reflect differences in the spatial distribution of signals within the limb bud mesoderm.…”

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confidence: 99%

Sox9 Expression in Amniotes: Species-Specific Differences in the Formation of Digits

Montero

Lorda‐Diez

Francisco-Morcillo

et al. 2017

Front. Cell Dev. Biol.

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In tetrapods the digit pattern has evolved to adapt to distinct locomotive strategies. The number of digits varies between species or even between hindlimb and forelimb within the same species. These facts illustrate the plasticity of embryonic limb autopods. Sox9 is a precocious marker of skeletal differentiation of limb mesenchymal cells. Its pattern of expression in the developing limb has been widely studied and reflects the activity of signaling cascades responsible for skeletogenesis. In this assay we stress previously overlooked differences in the pattern of expression of Sox9 in limbs of avian, mouse and turtle embryos which may reflect signaling differences associated with distinct limb skeletal morphologies observed in these species. Furthermore, we show that Sox9 gene expression is higher and maintained in the interdigital region in species with webbed digits in comparison with free digit animals.

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Retinoic acid regulates programmed cell death through BMP signalling

Cited by 92 publications

References 15 publications

Modulation of Bone Morphogenetic Protein (BMP) 2 gene expression by Sp1 transcription factors

Modulation of Bone Morphogenetic Protein (BMP) 2 gene expression by Sp1 transcription factors

Biology of Developmental and Regenerative Skeletogenesis

Sox9 Expression in Amniotes: Species-Specific Differences in the Formation of Digits

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