Osteogenesis 2 - Circulation - focuses on the key moment in life history of any cartilage model bone when bone first appears, the initiation of the primary center of ossification or PCO. The focus of the literature is that the cartilage in the model is replaced by endchondral bone formation. Careful analysis of the event shows that bone formation starts in two areas, one external to the cartilage model, wherein the cells in the cambium or germanitive layer of the periochondrium are influenced by vascular endothelial growth factor (VEGF) to change their nature. Some are influenced directly to become endothelial cells, and proliferate to develop an extenal circulatory bed supplying the tissues external to the model, as a bone collar develops first at the level of the hypertrophic cartilage cells (HCCS) external to the model. Influenced by VEGF, some of the cells transform to pre-osteoblasts and follow the pathway to become osteoblasts which make woven bone that rims the outside of the model. There is a tremendous surge of proliferation as waves of this "streamer bone" wrap around the model. Yet other external cells,monocytes, are also influenced by VEGF, M-CSF, and RANK to commit to becoming osteo- and chondro-clasts, whose role is to create a pathway for capillary invasion, vessels that become the nutrient vessel system that supplies the endosteum of the evolving bone. First, at one or more sites in the level of the middle of the model, osteoclasts delete woven bone creating an aperture known as the nutrient foramen, through which chondroclasts aggessively delete the calcified cartilage that forms as the cartilage cells undergo terminal differentiation, undergo apoptosis, and die. The problem with clasts is that they are very efficient; just one deletes three times its cell volume in just 1-2 days, and it takes 100-150 osteoblasts to make the bone that replaces that space over months. Clasts are evanescent. You do not see them as they are there and then gone. You see, however, their effect on bone and cartilage by the ragged edges of the cavities they create. Developing the complex circulation of a bone a question of geography. Where ever vessels go, clasts have to precede them because endothelial cells do not delete matrix. Only clasts can do that, and the matrix has to be either bone, or calcified cartilage. The sequence is the same externally forming periosteal blood supply, internally, the nutrient vessel system, in the metapysis, the metaphyseal vessels, and on either side of every joint forming the epiphyseal vessels. The details in these human embryological slides are fascinating, and are quite different from what is seen in animal models.
3 окт 2019
