Maturation of cortical bone suppresses periosteal osteoprogenitor proliferation in a paracrine manner
| Autor: | Chi-Young Yun, Byung-Hyun Park, Young Jae Moon, Jeong-Chae Lee, Jung Ryul Kim, Eui-Sic Cho |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Histology Physiology Mice Transgenic 030209 endocrinology & metabolism Bone healing Osteocytes Mice 03 medical and health sciences chemistry.chemical_compound Paracrine signalling Calcification Physiologic 0302 clinical medicine Osteogenesis Periosteum Internal medicine Paracrine Communication Cortical Bone medicine Animals Cell Proliferation Smad4 Protein Osteoblasts biology Stem Cells Wnt signaling pathway Cell Differentiation Osteoblast Cell Biology General Medicine Cell biology Wnt Proteins 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Sp7 Transcription Factor Gene Knockdown Techniques Gene Targeting Osteocalcin biology.protein Sclerostin Cortical bone Biomarkers Transcription Factors |
| Zdroj: | Journal of Molecular Histology. 47:445-453 |
| ISSN: | 1567-2387 1567-2379 |
| Popis: | Periosteum contains enriched pools of osteogenic progenitors and is highly proliferative, thus giving this tissue a pivotal role in maintaining the diameter of the diaphyseal cortex and in recovery from fractures. Although periosteal proliferation has not been detected in normal bone, intense periosteal proliferation has been observed in pathologic states such as fracture, inflammation, and bone tumors. However, the mechanism by which periosteal osteoprogenitor proliferation is regulated remains poorly understood. To investigate this regulation mechanism, osteoblast/osteocyte-specific conditional knockout mice were developed lacking Smad4 and Osx, two factors that are essential for osteoblast differentiation and matrix mineralization. In Smad4 (Col) and Osx (Col) mice, osteocalcin, Dmp-1, and sclerostin expression were significantly decreased in the cortical bone. Interestingly, although Cre activity was not observed in the periosteum, the proliferation of periosteal osteoprogenitors was enhanced in Smad4 (Col) and Osx (Col) mice, as assessed by 5'-bromo-2'deoxyuridine incorporation and proliferating cell nuclear antigen localization. Since Wnt signaling is a major factor affecting periosteal proliferation, we evaluated Wnt signaling in the periosteum. The expression levels of β-catenin and Lef-1 were increased in the periosteal osteoprogenitors. Moreover, the mRNA levels of β-catenin, cyclin D1, Lef-1, and Axin2, all of which are Wnt target genes, were significantly increased in the periosteum of both Smad4 (Col) and Osx (Col) mice. These results indicated that extracellular proteins secreted by mature osteoblasts and osteocytes suppress the proliferation of periosteal osteoprogenitors by blocking Wnt signaling in a paracrine manner. Our data suggest a new concept of periosteal bone healing and periosteal bone formation. |
| Databáze: | OpenAIRE |
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