12 nots - 1 Lecture 12 Notes October 22, 2008 The focus of...

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1 Lecture 12 Notes October 22, 2008 The focus of the first half of the lecture will be on the role of biglycan in promoting osteoblast differentiation. Hence, you need to know fundamentals about osteogenesis. Verbatim from Gilbert, Developmental Biology, 7th edition, Sinauer Associates, Inc. Osteogenesis: The development of bones Three distinct lineages generate the skeleton. The somites generate the axial (vertebrate) skeleton, the lateral plate mesoderm gives rise to the limb skeleton, and the cranial neural crest gives rise to the bronchial arch and craniofacial bones and cartilage. There are two major modes of bone formation, or Osteogenesis, and both involve the transformation of preexisting mesenchymal tissue into bone. The direct conversion of mesenchymal tissue into bone is called intramembranous (or dermal) ossification. In other cases, the mesenchyme cells differentiate into cartilage, which is formed and then replaced by bone cells is called endochondral ossification. Endochondral ossification is seen predominantly in the vertebral column, ribs, pelvis, and limbs. Endochondral ossification Endochondral ossification involves the formation of cartilage tissue from aggregated mesenchymal cells, and the subsequent replacement of cartilage tissue by bone. This type of bone formation is characteristic of vertebrate, ribs, and limbs. The vertebrae and ribs from somites, while the limb bones form from the lateral plate mesoderm. The process of endochondral ossification can divided into five stages. 1 st , the mesenchymal cells commit to become cartilage cells. This commitment is cause by sonic hedgehog (Shh), which induces the nearby sclerotome cells (somite origin) to express Pax1 transcription factor. Pax1 initiates a cascade that is dependent on external paracrine factors and internal transcription. During the 2 nd phase of endochondral ossification , the committed mesenchymal cells condense into compact nodules and differentiate into chondrocytes, the cartilage cells. BMPs appear to be critical in this stage. They are responsible for inducing the expression of the adhesion molecules N-cadherin and N-CAM and the transcription factor Sox9. N- cadherins appears to be important in the initiation of these condensations, and N-CAM seems to be critical for maintaining them. Sox9 activates other transcription factors as well as the genes encoding collagen 2 and aggrecan, which is critical in cartilage function. During the 3 rd phase of endochondral ossification , the chondrocytes proliferate rapidly to form the cartilage model of bone. As they divide, the chondrocytes secrete a cartilage-specific ECM. In the 4 th phase, the chondrocytes stop dividing and increase their volume dramatically, becoming hypertrophic chondrocytes. This step appears
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2 mediated by the transcription factor Runx2/Cbfa1, which is necessary for the development of both intramembranous and endochondral bones. The large chondrocytes alter the matrix to produced collagen X and fibronectin to enable
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This note was uploaded on 09/29/2009 for the course CSB csb327 taught by Professor Ringuitte during the Fall '08 term at University of Toronto.

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12 nots - 1 Lecture 12 Notes October 22, 2008 The focus of...

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