Genome complexity in embryology: bone manufacture (Introduction)

by David Turell , Monday, August 27, 2018, 19:35 (2067 days ago) @ David Turell

Complex in forming in the fetus and when repairing fractures:

https://medicalxpress.com/news/2018-08-art-bone.html

Cell differentiation is a widely studied phenomenon forming the basis of all developmental processes including fetal growth and bone fracture healing. A series of recent studies indicates the emerging role of chondrocyte-to-osteoblast transdifferentiation during bone tissue formation, known as endochondral ossification (replacing cartilage with bone).

While transdifferentiation is not a new phenomenon and occurs when mature cells switch from one differentiated phenotype to another, new data have identified three models for chondrocyte (cartilage) to osteoblast (bone) transdifferentiation during fracture healing. Now writing in Bone Research, Patrick Aghajanian and Subburaman Mohan have dissected the three emerging models and categorized them to better understand the process of bone building. The new knowledge will allow bioengineers in regenerative medicine to advance the molecular basis of bone repair.

During typical cell differentiation, programmed cells progress along a specific lineage until they reach an endpoint of terminal differentiation and apoptosis. Transdifferentiation does not follow the preprogrammed path, switching instead from one mature phenotype to another. Prior to assessing the newly discovered mechanisms of chondrocyte-to-osteoblast transdifferentiation, the authors first reviewed the traditional mechanism of endochondral ossification.

The typical process of replacing cartilage with bone is divided into primary and secondary pathways, beginning with a template of rapidly proliferating immature chondrocytes that secrete a collagen matrix. In the primary process, chondrocytes undergo differentiation to form the bone matrix, facilitate bone forming cells (mesenchymal stromal cells) to enter the process and differentiate into osteoblasts/osteocytes during embryogenesis, while the chondrocytes themselves become hypertrophic to undergo apoptosis. The secondary process occurs similarly but post-natally, during which immature chondrocytes become hypertrophic and undergo apoptosis, and the vasculature invades to transport marrow, mesenchymal stem cells and osteoclast precursors to initiate bone formation at the center and extend peripherally.

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While the exact cause for chondrocyte to osteoblast transdifferentiation is unknown, regulatory factors are necessary for that transition. Runx2 gene, for instance, is a master regulator of osteogenic fate, capable of transdifferentiating adipocytes, primary skeletal myoblasts, odontoblasts and vascular smooth muscle cells to osteogenic cell types. Studies with animal models are required to validate the contribution of various signaling pathways identified in in vitro studies during chondrocyte-to-osteoblast transdifferentiation.

Comment: Look at the diagrams to see the complexity. Not by chance.