Using the distance osteosynthesis model of the rabbit tibia the granulation tissue was investigated in the interfragmental gap and in tissue specimens from the adjacent bone marrow. Histological techniques and the method of indirect immunocytochemistry were applied to investigate the 5th, 10th, 15th, 20th and 25th postoperative day. Presursor cells of the osteotomy near bone marrow leave marks of CGRP and/or cytoplasmic SP-immunoreactivity at the 5th postoperative day. Imigrating into the granulation tissue of the interfragmental gap these cells showed intensive SP-immunoreactivity and form structures which can be supposed to be the angiogenic structure of the desmal ossification. Immunoreactive praeosteoblasts separate themselves from nonreactive endoluminal praeendothelial cells. Osteo- and vasculoneogenesis in the interfragmental gap starts from a homogenous population of precursor cells which are released from the bone marrow. A selective CGRP-immunoreactivity is typical in the migrating osteoblasts at the 15th postoperative day simultaneous to CGRP-positive nerves. On the 20th postoperative day only a few osteoblasts can be demonstrated which express this peptide. Neuropeptide SP and CGRP mark first steps of the osteogenic differentiation from the mesenchymal stem and/or osteoprogenitor cells which trace their origin back to the bone marrow. To begin with the CGRP-expression in these cells, the immunohistochemical proof emphasize the role of neuropeptides in the early phase of fracture healing.
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